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Chromosome

Chromosome.svg eukaryotic chromosome: 1. Chromatid

2. Centromere

3. Short arm

4. Long arm]]

A chromosome is a package of DNA with part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells the most important of these proteins are the histones. These proteins, aided by chaperone proteins, bind to and condense the DNA molecule to maintain its integrity. These chromosomes display a complex three-dimensional structure, which plays a significant role in transcriptional regulation.

Chromosomes are normally visible under a light microscope only during the metaphase of cell division (where all chromosomes are aligned in the center of the cell in their condensed form). Before this happens, each chromosome is duplicated (S phase), and both copies are joined by a centromere, resulting either in an X-shaped structure (pictured above), if the centromere is located equatorially, or a two-arm structure, if the centromere is located distally. The joined copies are now called sister chromatids. During metaphase, the X-shaped structure is called a metaphase chromosome, which is highly condensed and thus easiest to distinguish and study. In animal cells, chromosomes reach their highest compaction level in anaphase during chromosome segregation.

Chromosomal recombination during meiosis and subsequent sexual reproduction play a significant role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe. Usually, this will make the cell initiate apoptosis leading to its own death, but sometimes mutations in the cell hamper this process and thus cause progression of cancer.

Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation.

Etymology
The word chromosome comes from the Greek χρῶμα (chroma, "colour") and σῶμα (soma, "body"), describing their strong staining by particular dyes. The term was coined by the German anatomist Heinrich Wilhelm Waldeyer, referring to the term chromatin, which was introduced by Walther Flemming.

Some of the early karyological terms have become outdated. For example, Chromatin (Flemming 1880) and Chromosom (Waldeyer 1888), both ascribe color to a non-colored state.

History of discovery
Otto Bütschli was the first scientist to recognize the structures now known as chromosomes.

In a series of experiments beginning in the mid-1880s, Theodor Boveri gave definitive contributions to elucidating that chromosomes are the vectors of heredity, with two notions that became known as 'chromosome continuity' and 'chromosome individuality'.

Wilhelm Roux suggested that each chromosome carries a different genetic configuration, and Boveri was able to test and confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of Gregor Mendel's earlier work, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Nettie Stevens, Walter Sutton and Theophilus Painter were all influenced by Boveri (Wilson, Stevens, and Painter actually worked with him).

In his famous textbook The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton (both around 1902) by naming the chromosome theory of inheritance the Boveri–Sutton chromosome theory (the names are sometimes reversed). Ernst Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T.H. Morgan, all of a rather dogmatic turn of mind. Eventually, complete proof came from chromosome maps in Morgan's own lab.

The number of human chromosomes was published in 1923 by Theophilus Painter. By inspection through the microscope, he counted twenty-four pairs, which would mean forty-eight chromosomes. His error was copied by others and it was not until 1956 that the true number, forty-six, was determined by Indonesian-born cytogeneticist Joe Hin Tjio.

Prokaryotes
The prokaryotes – bacteria and archaea – typically have a single circular chromosome, but many variations exist. The chromosomes of most bacteria, which some authors prefer to call genophores, can range in size from only 130,000 base pairs in the endosymbiotic bacteria Candidatus Hodgkinia cicadicola and Candidatus Tremblaya princeps, to more than 14,000,000 base pairs in the soil-dwelling bacterium Sorangium cellulosum. Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome.

Structure in sequences
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria typically have a one-point (the origin of replication) from which replication starts, whereas some archaea contain multiple replication origins. The genes in prokaryotes are often organized in operons, and do not usually contain introns, unlike eukaryotes.

DNA packaging
Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid. The nucleoid is a distinct structure and occupies a defined region of the bacterial cell. This structure is, however, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome. In archaea, the DNA in chromosomes is even more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes.

Certain bacteria also contain plasmids or other extrachromosomal DNA. These are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. In prokaryotes (see nucleoids) and viruses, the DNA is often densely packed and organized; in the case of archaea, by homology to eukaryotic histones, and in the case of bacteria, by histone-like proteins.

Bacterial chromosomes tend to be tethered to the plasma membrane of the bacteria. In molecular biology application, this allows for its isolation from plasmid DNA by centrifugation of lysed bacteria and pelleting of the membranes (and the attached DNA).

Prokaryotic chromosomes and plasmids are, like eukaryotic DNA, generally supercoiled. The DNA must first be released into its relaxed state for access for transcription, regulation, and replication.

Eukaryotes

Each eukaryotic chromosome consists of a long linear DNA molecule associated with proteins, forming a compact complex of proteins and DNA called chromatin. Chromatin contains the vast majority of the DNA in an organism, but a small amount inherited maternally can be found in the mitochondria. It is present in most cells, with a few exceptions, for example, red blood cells.

Histones are responsible for the first and most basic unit of chromosome organization, the nucleosome.

Eukaryotes (cells with nuclei such as those found in plants, fungi, and animals) possess multiple large linear chromosomes contained in the cell's nucleus. Each chromosome has one centromere, with one or two arms projecting from the centromere, although, under most circumstances, these arms are not visible as such. In addition, most eukaryotes have a small circular mitochondrial genome, and some eukaryotes may have additional small circular or linear cytoplasmic chromosomes.

In the nuclear chromosomes of eukaryotes, the uncondensed DNA exists in a semi-ordered structure, where it is wrapped around histones (structural proteins), forming a composite material called chromatin.

Interphase chromatin
The packaging of DNA into nucleosomes causes a 10 nanometer fibre which may further condense up to 30 nm fibres Most of the euchromatin in interphase nuclei appears to be in the form of 30-nm fibers. Chromatin structure is the more decondensed state, i.e. the 10-nm conformation allows transcription.

During interphase (the period of the cell cycle where the cell is not dividing), two types of chromatin can be distinguished:
 * Euchromatin, which consists of DNA that is active, e.g., being expressed as protein.
 * Heterochromatin, which consists of mostly inactive DNA. It seems to serve structural purposes during the chromosomal stages. Heterochromatin can be further distinguished into two types:
 * Constitutive heterochromatin, which is never expressed. It is located around the centromere and usually contains repetitive sequences.
 * Facultative heterochromatin, which is sometimes expressed.

Metaphase chromatin and division

In the early stages of mitosis or meiosis (cell division), the chromatin double helix becomes more and more condensed. They cease to function as accessible genetic material (transcription stops) and become a compact transportable form. The loops of thirty-nanometer chromatin fibers are thought to fold upon themselves further to form the compact metaphase chromosomes of mitotic cells. The DNA is thus condensed about ten-thousand-fold.

The chromosome scaffold, which is made of proteins such as condensin, TOP2A and KIF4, plays an important role in holding the chromatin into compact chromosomes. Loops of thirty-nanometer structure further condense with scaffold into higher order structures.

This highly compact form makes the individual chromosomes visible, and they form the classic four-arm structure, a pair of sister chromatids attached to each other at the centromere. The shorter arms are called p arms (from the French petit, small) and the longer arms are called q arms (q follows p in the Latin alphabet; q-g "grande"; alternatively it is sometimes said q is short for queue meaning tail in French ). This is the only natural context in which individual chromosomes are visible with an optical microscope.

Mitotic metaphase chromosomes are best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.

During mitosis, microtubules grow from centrosomes located at opposite ends of the cell and also attach to the centromere at specialized structures called kinetochores, one of which is present on each sister chromatid. A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region. The microtubules then pull the chromatids apart toward the centrosomes, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and DNA can again be transcribed. In spite of their appearance, chromosomes are structurally highly condensed, which enables these giant DNA structures to be contained within a cell nucleus.

Human chromosomes
Chromosomes in humans can be divided into two types: autosomes (body chromosome(s)) and allosome (sex chromosome(s)). Certain genetic traits are linked to a person's sex and are passed on through the sex chromosomes. The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division. Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of the mitochondrial genome. Sequencing of the human genome has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on the Sanger Institute's human genome information in the Vertebrate Genome Annotation (VEGA) database. Number of genes is an estimate, as it is in part based on gene predictions. Total chromosome length is an estimate as well, based on the estimated size of unsequenced heterochromatin regions.

Based on the micrographic characteristics of size, position of the centromere and sometimes the presence of a chromosomal satellite, the human chromosomes are classified into the following groups:

Karyotype

In general, the karyotype is the characteristic chromosome complement of a eukaryote species. The preparation and study of karyotypes is part of cytogenetics.

Although the replication and transcription of DNA is highly standardized in eukaryotes, the same cannot be said for their karyotypes, which are often highly variable. There may be variation between species in chromosome number and in detailed organization. In some cases, there is significant variation within species. Often there is:
 * 1. variation between the two sexes
 * 2. variation between the germline and soma (between gametes and the rest of the body)
 * 3. variation between members of a population, due to balanced genetic polymorphism
 * 4. geographical variation between races
 * 5. mosaics or otherwise abnormal individuals.

Also, variation in karyotype may occur during development from the fertilized egg.

The technique of determining the karyotype is usually called karyotyping. Cells can be locked part-way through division (in metaphase) in vitro (in a reaction vial) with colchicine. These cells are then stained, photographed, and arranged into a karyogram, with the set of chromosomes arranged, autosomes in order of length, and sex chromosomes (here X/Y) at the end.

Like many sexually reproducing species, humans have special gonosomes (sex chromosomes, in contrast to autosomes). These are XX in females and XY in males.

History and analysis techniques
Investigation into the human karyotype took many years to settle the most basic question: How many chromosomes does a normal diploid human cell contain? In 1912, Hans von Winiwarter reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism. In 1922, Painter was not certain whether the diploid number of man is 46 or 48, at first favouring 46. He revised his opinion later from 46 to 48, and he correctly insisted on humans having an XX/XY system.

New techniques were needed to definitively solve the problem:
 * 1) Using cells in culture
 * 2) Arresting mitosis in metaphase by a solution of colchicine
 * 3) Pretreating cells in a hypotonic solution 0.075 M KCl, which swells them and spreads the chromosomes
 * 4) Squashing the preparation on the slide forcing the chromosomes into a single plane
 * 5) Cutting up a photomicrograph and arranging the result into an indisputable karyogram.

It took until 1954 before the human diploid number was confirmed as 46. Considering the techniques of Winiwarter and Painter, their results were quite remarkable. Chimpanzees, the closest living relatives to modern humans, have 48 chromosomes as do the other great apes: in humans two chromosomes fused to form chromosome 2.

Aberrations

Chromosomal aberrations are disruptions in the normal chromosomal content of a cell. They can cause genetic conditions in humans, such as Down syndrome, although most aberrations have little to no effect. Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of bearing a child with a chromosome disorder. Abnormal numbers of chromosomes or chromosome sets, called aneuploidy, may be lethal or may give rise to genetic disorders. Genetic counseling is offered for families that may carry a chromosome rearrangement.

The gain or loss of DNA from chromosomes can lead to a variety of genetic disorders. Human examples include:
 * Cri du chat, which is caused by the deletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French; the condition was so-named because affected babies make high-pitched cries that sound like those of a cat. Affected individuals have wide-set eyes, a small head and jaw, moderate to severe mental health problems, and are very short.
 * Down syndrome, the most common trisomy, usually caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, stockier build, asymmetrical skull, slanting eyes and mild to moderate developmental disability.
 * Edwards syndrome, or trisomy-18, the second most common trisomy. Symptoms include motor retardation, developmental disability and numerous congenital anomalies causing serious health problems. Ninety percent of those affected die in infancy. They have characteristic clenched hands and overlapping fingers.
 * Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15).
 * Jacobsen syndrome, which is very rare. It is also called the 11q terminal deletion disorder. Those affected have normal intelligence or mild developmental disability, with poor expressive language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.
 * Klinefelter syndrome (XXY). Men with Klinefelter syndrome are usually sterile and tend to be taller and have longer arms and legs than their peers. Boys with the syndrome are often shy and quiet and have a higher incidence of speech delay and dyslexia. Without testosterone treatment, some may develop gynecomastia during puberty.
 * Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, without the characteristic folded hand.
 * Small supernumerary marker chromosome. This means there is an extra, abnormal chromosome. Features depend on the origin of the extra genetic material. Cat-eye syndrome and isodicentric chromosome 15 syndrome (or Idic15) are both caused by a supernumerary marker chromosome, as is Pallister–Killian syndrome.
 * Triple-X syndrome (XXX). XXX girls tend to be tall and thin and have a higher incidence of dyslexia.
 * Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. Females with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved-in" appearance to the chest.
 * Wolf–Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. It is characterized by growth retardation, delayed motor skills development, "Greek Helmet" facial features, and mild to profound mental health problems.
 * XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are more likely to have learning difficulties.

Sperm aneuploidy
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. In particular, risk of aneuploidy is increased by tobacco smoking, and occupational exposure to benzene, insecticides,  and perfluorinated compounds. Increased aneuploidy is often associated with increased DNA damage in spermatozoa.

In eukaryotes
The number of chromosomes in eukaryotes is highly variable (see table). In fact, chromosomes can fuse or break and thus evolve into novel karyotypes. Chromosomes can also be fused artificially. For example, the 16 chromosomes of yeast have been fused into one giant chromosome and the cells were still viable with only somewhat reduced growth rates.

The tables below give the total number of chromosomes (including sex chromosomes) in a cell nucleus. For example, most eukaryotes are diploid, like humans who have 22 different types of autosomes, each present as two homologous pairs, and two sex chromosomes. This gives 46 chromosomes in total. Other organisms have more than two copies of their chromosome types, such as bread wheat, which is hexaploid and has six copies of seven different chromosome types – 42 chromosomes in total.

Normal members of a particular eukaryotic species all have the same number of nuclear chromosomes (see the table). Other eukaryotic chromosomes, i.e., mitochondrial and plasmid-like small chromosomes, are much more variable in number, and there may be thousands of copies per cell.

Asexually reproducing species have one set of chromosomes that are the same in all body cells. However, asexual species can be either haploid or diploid.

Sexually reproducing species have somatic cells (body cells), which are diploid [2n] having two sets of chromosomes (23 pairs in humans), one set from the mother and one from the father. Gametes, reproductive cells, are haploid [n]: They have one set of chromosomes. Gametes are produced by meiosis of a diploid germline cell. During meiosis, the matching chromosomes of father and mother can exchange small parts of themselves (crossover), and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge (fertilization), a new diploid organism is formed.

Some animal and plant species are polyploid [Xn]: They have more than two sets of homologous chromosomes. Plants important in agriculture such as tobacco or wheat are often polyploid, compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some cultivars as well as the wild progenitors. The more-common pasta and bread wheat types are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to the 14 (diploid) chromosomes in the wild wheat.

In prokaryotes
Prokaryote species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies. For example, Buchnera, a symbiont of aphids has multiple copies of its chromosome, ranging from 10–400 copies per cell. However, in some large bacteria, such as Epulopiscium fishelsoni up to 100,000 copies of the chromosome can be present. Plasmids and plasmid-like small chromosomes are, as in eukaryotes, highly variable in copy number. The number of plasmids in the cell is almost entirely determined by the rate of division of the plasmid – fast division causes high copy number.

title: Chromosome


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Charge

Charge or charged may refer to:

Films

 * Charge, Zero Emissions/Maximum Speed, a 2011 documentary

Music

 * Charge (David Ford album)
 * Charge (Machel Montano album)
 * Charge!!, an album by The Aquabats
 * Charged (Nebula album)
 * Charged (Toshinori Kondo, Eraldo Bernocchi and Bill Laswell album)

Television

 * Charge (TV series)
 * Charge! (TV network)
 * "Charged" (Reaper), episode 2 of season one of Reaper

Companies

 * Charge Automotive Limited, an electric-vehicle manufacturer
 * Charged Productions, an animation studio
 * Charged Records, a record label

Finance

 * Equitable charge, confers a right on the secured party to look to a particular asset in the event of the debtor's default
 * Floating charge, a security interest over the assets of a company

Law

 * Criminal charge, a formal accusation made before a court by a prosecuting authority
 * Legal charge, information or indictment through a formal legal process

Mathematics, science, and technology

 * Charge (physics), the susceptibility (state of being affected) of a body to one of the fundamental forces
 * Color charge, a property of quarks and gluons, related to their strong interactions
 * Electric charge, a property which determines the electromagnetic interaction of subatomic particles
 * Magnetic charge, a property of theoretical magnetic monopoles
 * Charge, the air and fuel mixture fed into an internal combustion engine
 * CHARGE syndrome, a specific set of birth defects in children
 * Explosive charge, a measured quantity of explosive material
 * Signed, finitely additive measure in mathematics

Military and iconography

 * Charge (bugle call)
 * Charge (warfare), a military manoeuvre
 * Charges (military), ranks used in German-speaking armies
 * Charge (heraldry), any object depicted on a shield

Sports

 * Charge (basketball), illegal contact by pushing or moving into another player's torso
 * Charge (ice hockey), illegal contact by taking three or more strides or jumping before hitting an opponent
 * Charge (fanfare), played at sporting events
 * Guangzhou Charge, a Chinese esports team in the Overwatch League

Other uses

 * Charge of the Goddess, a text often used in the religion Wicca
 * Charge (student associations), the executive of German student fraternities
 * Charge (youth), an underage person placed in the care of a medieval nobleman
 * Charge, a type of pen spinning trick
 * Chargé d'affaires, two classes of diplomatic agents
 * Pastoral charge, a group of congregants in some Protestant churches

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Charge


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Colonna family

The House of Colonna, also known as Sciarrillo or Sciarra, is an Italian noble family, forming part of the papal nobility. It was powerful in medieval and Renaissance Rome, supplying one pope (Martin V) and many other church and political leaders. The family is notable for its bitter feud with the Orsini family over influence in Rome, until it was stopped by papal bull in 1511. In 1571, the heads of both families married nieces of Pope Sixtus V. Thereafter, historians recorded that "no peace had been concluded between the princes of Christendom, in which they had not been included by name".

Origins
According to tradition, the Colonna family is a branch of the Counts of Tusculum — by Peter (1099–1151) son of Gregory III, called Peter "de Columna" from his property the Columna Castle in Colonna, in the Alban Hills. Further back, they trace their lineage past the Counts of Tusculum via Lombard and Italo-Roman nobles, merchants, and clergy through the Early Middle Ages — ultimately claiming origins from the Julio-Claudian dynasty and the gens Julia whose origin is lost in the mists of time but which entered the annals for the first time in 489 BC with the consulship of Gaius Julius Iulus.

The first cardinal from the family was appointed in 1206, when Giovanni Colonna di Carbognano was made Cardinal Deacon of SS. Cosma e Damiano. For many years, Cardinal Giovanni di San Paolo (elevated in 1193) was identified as a member of the Colonna family and therefore its first representative in the College of Cardinals, but modern scholars have established that this was based on false information from the beginning of the 16th century.

Giovanni Colonna (born c. 1206) nephew of Cardinal Giovanni Colonna di Carbognano, made his solemn vows as a Dominican around 1228 and received his theological and philosophical training at the Roman studium of Santa Sabina, the forerunner of the Pontifical University of Saint Thomas Aquinas, Angelicum. He served as the Provincial of the Roman province of the Dominican Order and led the provincial chapter of 1248 at Anagni. Colonna was appointed as Archbishop of Messina in 1255.

Margherita Colonna (died 1248) was a member of the Franciscan Order. She was beatified by Pope Pius IX in 1848. At this time, a rivalry began with the pro-papal Orsini family, leaders of the Guelph faction. This reinforced the pro-Emperor Ghibelline course that the Colonna family followed throughout the period of conflict between the Papacy and the Holy Roman Empire. Ironically according to their own family legend, the Orsini are also descended from the Julio-Claudian dynasty of ancient Rome.

Colonna versus Papacy
In 1297, Cardinal Jacopo disinherited his brothers Ottone, Matteo, and Landolfo of their lands. The latter three appealed to Pope Boniface VIII, who ordered Jacopo to return the land, and furthermore hand over the family's strongholds of Colonna, Palestrina, and other towns to the Papacy. Jacopo refused; in May, Boniface removed him from the College of Cardinals and excommunicated him and his followers.

The Colonna family (aside from the three brothers allied with the Pope) declared that Boniface had been elected illegally following the unprecedented abdication of Pope Celestine V. The dispute led to open warfare, and in September, Boniface appointed Landolfo to the command of his army, to put down the revolt of Landolfo's own Colonna relatives. By the end of 1298, Landolfo had captured Colonna, Palestrina and other towns, and razed them to the ground. The family's lands were distributed among Landolfo and his loyal brothers; the rest of the family fled Italy.

The exiled Colonnas allied with the Pope's other great enemy, Philip IV of France, who in his youth had been tutored by Cardinal Egidio Colonna. In September 1303, Sciarra and Philipp's advisor, Guillaume de Nogaret, led a small force into Anagni to arrest Boniface VIII and bring him to France, where he was to stand trial. The two managed to apprehend the pope, and Sciarra reportedly slapped the pope in the face in the process, which was accordingly dubbed the "Outrage of Anagni". The attempt eventually failed after a few days, when locals freed the pope. However, Boniface VIII died on 11 October, allowing France to dominate his weaker successors during the Avignon papacy.

Late Middle Ages
The family remained at the centre of civic and religious life throughout the late Middle Ages. Cardinal Egidio Colonna died at the papal court in Avignon in 1314. An Augustinian, he had studied theology in Paris under St. Thomas of Aquinas to become one of the most authoritative thinkers of his time.

In the 14th century, the family sponsored the decoration of the Church of San Giovanni, most notably the floor mosaics.

In 1328, Louis IV of Germany marched into Italy for his coronation as Holy Roman Emperor. As Pope John XXII was residing in Avignon and had publicly declared that he would not crown Louis, the King decided to be crowned by a member of the Roman aristocracy, who proposed Sciarra Colonna. In honor of this event, the Colonna family was granted the privilege of using the imperial pointed crown on top of their coat of arms.

The celebrated poet Petrarch, was a great friend of the family, in particular of Giovanni Colonna and often lived in Rome as a guest of the family. He composed a number of sonnets for special occasions within the Colonna family, including "Colonna the Glorious, the great Latin name upon which all our hopes rest". In this period, the Colonna started claiming they were descendants of the Julio-Claudian dynasty.

At the Council of Constance, the Colonna finally succeeded in their papal ambitions when Oddone Colonna was elected on 14 November 1417. As Martin V, he reigned until his death on 20 February 1431.

Early modern period
Vittoria Colonna became famous in the sixteenth century as a poet and a figure in literate circles.

In 1627 Anna Colonna, daughter of Filippo I Colonna, married Taddeo Barberini of the family Barberini; nephew of Pope Urban VIII.

In 1728, the Carbognano branch (Colonna di Sciarra) of the Colonna family added the name Barberini to its family name when Giulio Cesare Colonna di Sciarra married Cornelia Barberini, daughter of the last male Barberini to hold the name and granddaughter of Maffeo Barberini (son of Taddeo Barberini).

Current status
The Colonna family have been Prince Assistants to the Papal Throne since 1710, though their papal princely title only dates from 1854.

The family residence in Rome, the Palazzo Colonna, is open to the public every Saturday morning.

The main 'Colonna di Paliano' line is represented today by Prince Marcantonio Colonna di Paliano, Prince and Duke of Paliano (b. 1948), whose heir is Don Giovanni Andrea Colonna di Paliano (b. 1975), and by Don Prospero Colonna di Paliano, Prince of Avella (b. 1956), whose heir is Don Filippo Colonna di Paliano (b. 1995).

The 'Colonna di Stigliano' line is represented by Don Prospero Colonna di Stigliano, Prince of Stigliano (b. 1938), whose heir is his nephew Don Stefano Colonna di Stigliano (b. 1975) principe frederico giuseppe born 1954

Notable members

 * Blessed Margherita Colonna (c. 1255 – 1280)
 * Stefano Colonna (1265 – c. 1348), an influential noble in Medieval Rome and Imperial vicar in the early 14th century
 * Jacopo Colonna (1250–1318), cardinal
 * Giacomo Colonna (1270–1329), who took part in the Outrage of Anagni against Pope Boniface VIII
 * Giovanni Colonna (1295–1348), influential cardinal during the Avignon papacy
 * Oddone Colonna (1369–1431), whose election as Pope Martin V in 1417 ended the Western Schism
 * Ludovico Colonna (1390-1436), condottiero
 * Prospero I Colonna (1410–1463), cardinal
 * Fabrizio Colonna (c. 1450 – 1520), the father of Vittoria Colonna, and a general in the Holy League
 * Prospero Colonna (1452–1523), who fought alongside his cousin Fabrizio Colonna
 * Francesco Colonna (1453? – 1517?) [La "Pugna d'amore in sogno" di Francesco Colonna Romano, 1996, Maurizio Calvesi], who was credited (along with the monk Francesco Colonna) with the authorship of the Hypnerotomachia Poliphili by an acrostic in the text; also believed to have written the story
 * Marcantonio I Colonna (1478–1522), condottiero of the 15th–16th centuries
 * Pompeo Colonna (1479–1532), cardinal, a nephew of Prospero Colonna, mentioned above. Viceroy of Naples from 1530 to 1532
 * Vittoria Colonna (1490–1547), friend of Michelangelo. Married in 1507 the Spanish-Italian Fernando d'Avalos, marquis of Pescara (deceased 1525), adopting (on becoming a widow) Alfonso d'Avalos, also marquis del Vasto, a nephew of her former husband
 * Pirro Colonna (1500–1552), 16th century captain under Charles V, Holy Roman Emperor
 * Marco Antonio Colonna (1523–1597), cardinal
 * Marcantonio II Colonna the Younger (1535–1584), Duke of Tagliacozzo. Son of Ascanio Colonna and Juana de Aragón. He participated in the naval Battle of Lepanto against the Turks, 7 October 1571 and was Viceroy of Sicily in 1577–1584. Prince of Paliano.
 * Ascanio Colonna (1560–1608), cardinal
 * Federico Colonna y Tomacelli, Prince of Butera (1601–1641), Viceroy of Valencia, in Spain, 1640–1641, Viceroy of Catalonia, 1641. He was Great Constable of the kingdom of Naples (1639–1641) as had been his father Filippo I Colonna, (1578 – 11 April 1639).
 * Marcantonio V Colonna (1606/1610–1659), Prince of Paliano
 * Lorenzo Onofrio Colonna, Viceroy of Aragon, 1678–1681, in Spain
 * Prospero II Colonna (1662–1743), cardinal
 * Carlo Colonna (1665–1739), cardinal, created by Clement XI in 1706
 * Marcantonio Colonna (1724-1793), cardinal
 * Giovanni Antonio Colonna (1878–1940), politician
 * Guido Colonna di Paliano (1908–1982), diplomat and European Commissioner

title: Colonna family


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Ceuta

Ceuta (,, ; ; سَبْتَة) is an autonomous city of Spain on the North African coast.

Bordered by Morocco, it lies along the boundary between the Mediterranean Sea and the Atlantic Ocean. Ceuta is one of the special member state territories of the European Union, and it is one of several Spanish territories in Africa, which include Melilla and the Canary Islands. It was a regular municipality belonging to the province of Cádiz prior to the passing of its Statute of Autonomy in March 1995, as provided by the Spanish Constitution, henceforth becoming an autonomous city.

Ceuta, like Melilla and the Canary Islands, was classified as a free port before Spain joined the European Union. Its population is predominantly Christian and Muslim, with a small minority of Sephardic Jews and Sindhi Hindus, from Pakistan.

Spanish is the official language. Spanish and Darija Arabic are the two main spoken languages.

Names
The name Abyla has been said to have been a Punic name ("Lofty Mountain" or "Mountain of God") for Jebel Musa, the southern Pillar of Hercules. The name of the mountain was in fact Habenna (, ʾbn, "Stone" or "Stele") or ʾAbin-ḥīq (𐤀𐤁𐤍𐤇𐤒, ʾbnḥq, "Rock of the Bay"), about the nearby Bay of Benzú. The name was hellenized variously as Ápini (Ἄπινι), Abýla (Ἀβύλα), Abýlē (Ἀβύλη), Ablýx (Ἀβλύξ), and Abilē Stḗlē (Ἀβίλη Στήλη, "Pillar of Abyla") and in Latin as Abyla Mons ("Mount Abyla") or Abyla Columna ("the Pillar of Abyla").

The settlement below Jebel Musa was later renamed for the seven hills around the site, collectively referred to as the "Seven Brothers" (Ἑπτάδελφοι; Septem Fratres). In particular, the Roman stronghold at the site took the name "Fort at the Seven Brothers" (Castellum ad Septem Fratres). This was gradually shortened to Septem (Σέπτον Sépton) or, occasionally, Septum or Septa. These clipped forms continued as Berber Sebta and Arabic Sabtan or Sabtah (سبتة), which themselves became Ceuta in Portuguese and Spanish (locally ).

Ancient
Controlling access between the Atlantic Ocean and the Mediterranean Sea, the Strait of Gibraltar is an important military and commercial chokepoint. The Phoenicians realized the extremely narrow isthmus joining the Peninsula of Almina to the African mainland made Ceuta eminently defensible and established an outpost there early in the 1st millenniumBC. The Greek geographers record it by variations of Abyla, the ancient name of nearby Jebel Musa. Beside Calpe, the other Pillar of Hercules now known as the Rock of Gibraltar, the Phoenicians established Kart at what is now San Roque, Spain. Other good anchorages nearby became Phoenician and then Carthaginian ports at what are now Tangiers and Cádiz.

After Carthage's destruction in the Punic Wars, most of northwest Africa was left to the Roman client states of Numidia and—around Abyla—Mauretania. Punic culture continued to thrive in what the Romans knew as "Septem". After the Battle of Thapsus in 46 BC, Caesar and his heirs began annexing North Africa directly as Roman provinces but, as late as Augustus, most of Septem's Berber residents continued to speak and write in Punic.

Caligula assassinated the Mauretanian king Ptolemy in AD40 and seized his kingdom, which Claudius organized in AD 42, placing Septem in the province of Tingitana and raising it to the level of a colony. It subsequently was Romanized and thrived into the late 3rd century, trading heavily with Roman Spain and becoming well known for its salted fish. Roads connected it overland with Tingis (Tangiers) and Volubilis. Under Theodosius I in the late 4th century, Septem still had 10,000 inhabitants, nearly all Christian citizens speaking African Romance, a local dialect of Latin.

Medieval
Vandals, probably invited by Count Boniface as protection against the empress dowager, crossed the strait near Tingis around 425 and swiftly overran Roman North Africa. Their king, Gaiseric, focused his attention on the rich lands around Carthage; although the Romans eventually accepted his conquests and he continued to raid them anyway, he soon lost control of Tingis and Septem in a series of Berber revolts. When Justinian decided to reconquer the Vandal lands, his victorious general Belisarius continued along the coast, making Septem a westernmost outpost of the Byzantine Empire around 533. Unlike the former ancient Roman administration, however, Eastern Rome did not push far into the hinterland and made the more defensible Septem their regional capital in place of Tingis.

Epidemics, less capable successors and overstretched supply lines forced a retrenchment and left Septem isolated. It is likely that its count (comes) was obliged to pay homage to the Visigoth Kingdom in Spain in the early 7th century. There are no reliable contemporary accounts of the end of the Islamic conquest of the Maghreb around 710. Instead, the rapid Muslim conquest of Spain produced romances concerning Count Julian of Septem and his betrayal of Christendom in revenge for the dishonor that befell his daughter at King Roderick's court. Allegedly with Julian's encouragement and instructions, the Berber convert and freedman Tariq ibn Ziyad took his garrison from Tangiers across the strait and overran the Spanish so swiftly that both he and his master Musa bin Nusayr fell afoul of a jealous caliph, who stripped them of their wealth and titles.

After the death of Julian, sometimes also described as a king of the Ghomara Berbers, Berber converts to Islam took direct control of what they called Sebta. It was then destroyed during their great revolt against the Umayyad Caliphate around 740. Sebta subsequently remained a small village of Muslims and Christians surrounded by ruins until its resettlement in the 9th century by Mâjakas, chief of the Majkasa Berber tribe, who started the short-lived Banu Isam dynasty. His great-grandson briefly allied his tribe with the Idrisids, but Banu Isam rule ended in 931 when he abdicated in favor of Abd ar-Rahman III, the Umayyad ruler of Córdoba, Spain.

Chaos ensued with the fall of the Caliphate of Córdoba in 1031. Following this, Ceuta and Muslim Iberia were controlled by successive North African dynasties. Starting in 1084, the Almoravid Berbers ruled the region until 1147, when the Almohads conquered the land. Apart from Ibn Hud's rebellion in 1232, they ruled until the Tunisian Hafsids established control. The Hafsids' influence in the west rapidly waned, and Ceuta's inhabitants eventually expelled them in 1249. After this, a period of political instability persisted, under competing interests from the Marinids and Granada as well as autonomous rule under the native Banu al-Azafi. The Fez finally conquered the region in 1387, with assistance from Aragon.

Portuguese
On the morning of 21 August 1415, King John I of Portugal led his sons and their assembled forces in a surprise assault that would come to be known as the Conquest of Ceuta. The battle was almost anticlimactic, because the 45,000 men who traveled on 200 Portuguese ships caught the defenders of Ceuta off guard and suffered only eight casualties. By nightfall the town was captured. On the morning of 22 August, Ceuta was in Portuguese hands. Álvaro Vaz de Almada, 1st Count of Avranches was asked to hoist what was to become the flag of Ceuta, which is identical to the flag of Lisbon, but in which the coat of arms derived from that of the Kingdom of Portugal was added to the center; the original Portuguese flag and coat of arms of Ceuta remained unchanged, and the modern-day Ceuta flag features the configuration of the Portuguese shield.

John's son Henry the Navigator distinguished himself in the battle, being wounded during the conquest. The looting of the city proved to be less profitable than expected for John I, so he decided to keep the city to pursue further enterprises in the area.

From 1415 to 1437, Pedro de Meneses became the first governor of Ceuta.

The Marinid Sultanate started the 1419 siege but was defeated by the first governor of Ceuta before reinforcements arrived in the form of John, Constable of Portugal and his brother Henry the Navigator, who were sent with troops to defend Ceuta.

Under King John I's son, Duarte, the colony at Ceuta rapidly became a drain on the Portuguese treasury. Trans-Saharan trade journeyed instead to Tangier. It was soon realized that without the city of Tangier, possession of Ceuta was worthless. In 1437, Duarte's brothers Henry the Navigator and Fernando, the Saint Prince persuaded him to launch an attack on the Marinid sultanate. The resulting Battle of Tangier (1437), led by Henry, was a debacle. In the resulting treaty, Henry promised to deliver Ceuta back to the Marinids in return for allowing the Portuguese army to depart unmolested, which he reneged on.

Possession of Ceuta indirectly led to further Portuguese expansion. The main area of Portuguese expansion, at this time, was the coast of the Maghreb, where there was grain, cattle, sugar, and textiles, as well as fish, hides, wax, and honey.

Ceuta had to endure alone for 43 years, until the position of the city was consolidated with the taking of Ksar es-Seghir (1458), Arzila and Tangier (1471) by the Portuguese.

The city was recognized as a Portuguese possession by the Treaty of Alcáçovas (1479) and by the Treaty of Tordesillas (1494).

In the 1540s the Portuguese began building the Royal Walls of Ceuta as they are today including bastions, a navigable moat and a drawbridge. Some of these bastions are still standing, like the bastions of Coraza Alta, Bandera and Mallorquines.

Luís de Camões lived in Ceuta between 1549 and 1551, losing his right eye in battle, which influenced his work of poetry Os Lusíadas.

Iberian Union
In 1578 King Sebastian of Portugal died at the Battle of Alcácer Quibir (known as the Battle of Three Kings) in what is today northern Morocco, without descendants, triggering the 1580 Portuguese succession crisis. His granduncle, the elderly Cardinal Henry, succeeded him as King, but Henry also had no descendants, having taken holy orders. When the cardinal-king died two years after Sebastian's death, three grandchildren of King Manuel I of Portugal claimed the throne:
 * Infanta Catarina, Duchess of Braganza
 * António, Prior of Crato
 * Philip II of Spain, uncle of former King Sebastian of Portugal

Philip prevailed and was crowned King Philip I of Portugal in 1581, uniting the two crowns and overseas empires in what is historically referred to as the Iberian Union.

During the Iberian Union, 1580 to 1640, Ceuta attracted many settlers of Spanish origin and became the only city of the Portuguese Empire that sided with Spain when Portugal regained its independence in the Portuguese Restoration War of 1640.

Spanish
On 1 January 1668, King Afonso VI of Portugal recognised the formal allegiance of Ceuta to Spain and ceded Ceuta to King Carlos II of Spain by the Treaty of Lisbon.

The city was attacked by Moroccan forces under Moulay Ismail during the Siege of Ceuta (1694–1727). During the longest siege in history, the city underwent changes leading to the loss of its Portuguese character. While most of the military operations took place around the Royal Walls of Ceuta, there were also small-scale penetrations by Spanish forces at various points on the Moroccan coast, and seizure of shipping in the Strait of Gibraltar.

During the Napoleonic Wars (1803-1815), Spain allowed Britain to occupy Ceuta. Occupation began in 1810, with Ceuta being returned at the conclusion of the wars.

Disagreements regarding the border of Ceuta resulted in the Hispano-Moroccan War (1859–60), which ended at the Battle of Tetuán.

In July 1936, General Francisco Franco took command of the Spanish Army of Africa and rebelled against the Spanish republican government; his military uprising led to the Spanish Civil War of 1936–1939. Franco transported troops to mainland Spain in an airlift using transport aircraft supplied by Germany and Italy. Ceuta became one of the first battlegrounds of the uprising: General Franco's rebel nationalist forces seized Ceuta, while at the same time the city came under fire from the air and sea forces of the official republican government.

The Llano Amarillo monument was erected to honor Francisco Franco, it was inaugurated on 13 July 1940. The tall obelisk has since been abandoned, but the shield symbols of the Falange and Imperial Eagle remain visible.

Following the 1947 Partition of India, a substantial number of Sindhi Hindus from current-day Pakistan settled in Ceuta, adding to a small Hindu community that had existed in Ceuta since 1893, connected to Gibraltar's.

When Spain recognized the independence of Spanish Morocco in 1956, Ceuta and the other plazas de soberanía remained under Spanish rule. Spain considered them integral parts of the Spanish state, but Morocco has disputed this point.

Culturally, modern Ceuta is part of the Spanish region of Andalusia. It was attached to the province of Cádiz until 1925, the Spanish coast being only 20 km (12.5 miles) away. It is a cosmopolitan city, with a large ethnic Arab-Berber Muslim minority as well as Sephardic Jewish and Hindu minorities.

On 5 November 2007, King Juan Carlos I visited the city, sparking great enthusiasm from the local population and protests from the Moroccan government. It was the first time a Spanish head of state had visited Ceuta in 80 years.

Since 2010, Ceuta (and Melilla) have declared the Muslim holiday of Eid al-Adha, or Feast of the Sacrifice, an official public holiday. It is the first time a non-Christian religious festival has been officially celebrated in Spanish ruled territory since the Reconquista.

Geography
Ceuta is separated by 17 km from the province of Cádiz on the Spanish mainland by the Strait of Gibraltar and it shares a 6.4 km land border with M'diq-Fnideq Prefecture in the Kingdom of Morocco. It has an area of 18.5 km2. It is dominated by Monte Anyera, a hill along its western frontier with Morocco, which is guarded by a Spanish military fort. Monte Hacho on the Peninsula of Almina overlooking the port is one of the possible locations of the southern pillar of the Pillars of Hercules of Greek legend (the other possibility being Jebel Musa).

Important Bird Area
The Ceuta Peninsula has been recognised as an Important Bird Area (IBA) by BirdLife International because the site is part of a migratory bottleneck, or choke point, at the western end of the Mediterranean for large numbers of raptors, storks and other birds flying between Europe and Africa. These include European honey buzzards, black kites, short-toed snake eagles, Egyptian vultures, griffon vultures, black storks, white storks and Audouin's gulls.

Climate
Ceuta has a maritime-influenced Mediterranean climate, similar to nearby Spanish and Moroccan cities such as Tarifa, Algeciras or Tangiers. The average diurnal temperature variation is relatively low; the average annual temperature is 18.8 C with average yearly highs of 21.4 C and lows of 15.7 C though the Ceuta weather station has only been in operation since 2003. Ceuta has relatively mild winters for the latitude, while summers are warm yet milder than in the interior of Southern Spain, due to the moderating effect of the Straits of Gibraltar. Summers are very dry, but yearly precipitation is still at 849 mm, which could be considered a humid climate if the summers were not so arid.

Government and administration

Since 1995, Ceuta is, along with Melilla, one of the two autonomous cities of Spain.

Ceuta is known officially in Spanish as Ciudad Autónoma de Ceuta (English: Autonomous City of Ceuta), with a rank between a standard municipality and an autonomous community. Ceuta is part of the territory of the European Union. The city was a free port before Spain joined the European Union in 1986. Now it has a low-tax system within the Economic and Monetary Union of the European Union.

Since 1979, Ceuta has held elections to its 25-seat assembly every four years. The leader of its government was the Mayor until the Autonomy Statute provided for the new title of Mayor-President. , the People's Party (PP) won 18 seats, keeping Juan Jesús Vivas as Mayor-President, which he has been since 2001. The remaining seats are held by the regionalist Caballas Coalition (4) and the Socialist Workers' Party (PSOE, 3).

Owing to its small population, Ceuta elects only one member of the Congress of Deputies, the lower house of the Cortes Generales (the Spanish Parliament). election, this post is held by María Teresa López of Vox.

Ceuta is subdivided into 63 barriadas ("neighborhoods"), such as Barriada de Berizu, Barriada de P. Alfonso, Barriada del Sarchal, and El Hacho.

Ceuta maintains its own police force.

Defence and Civil Guard
The defence of the enclave is the responsibility of the Spanish Armed Forces' General Command of Ceuta (COMGECEU). The Spanish Army's combat components of the command include:

 * 54th Regulares Infantry Regiment based in González Tablas barracks;
 * 2nd Tercio Duke of Alba Regiment of the Spanish Legion based in the Seraglio-Recarga cantonment;
 * 3rd "Montesa" Cavalry Regiment (RC-3) located in the Colonel Galindo barracks and equipped with Leopard 2 main battle tanks and Pizarro infantry fighting vehicles
 * 30th Mixed Artillery Regiment, one group equipped with 155/52mm towed howitzers and the other with Mistral short-range SAMs and 35/90 SKYDOR/35/90 GDF-007 anti-aircraft guns fulfilling an air defence role; and
 * 7th Engineer Regiment

The command also includes its headquarters battalion as well as logistics elements.

In 2023, the Spanish Navy replaced the Aresa-class patrol boat P-114 in the territory with the Rodman-class patrol boat Isla de León.

Ceuta itself is only 113 km distant from the main Spanish naval base at Rota on the Spanish mainland. The Spanish Air Force's Morón Air Base is also within 135 km proximity.

The Civil Guard is responsible for border security and protects both the territory's fortified land border as well as its maritime approaches against frequent, and sometimes significant, migrant incursions.

Economy

The official currency of Ceuta is the euro. It is part of a special low tax zone in Spain. Ceuta is one of two Spanish port cities on the northern shore of Africa, along with Melilla. They are historically military strongholds, free ports, oil ports, and also fishing ports. Today the economy of the city depends heavily on its port (now in expansion) and its industrial and retail centres. Ceuta Heliport is now used to connect the city to mainland Spain by air. Lidl, Decathlon and El Corte Inglés have branches in Ceuta. There is also a casino. Border trade between Ceuta and Morocco is active because of advantage of tax-free status. Thousands of Moroccan women are involved in the cross-border porter trade daily, as porteadoras. The Moroccan dirham is used in such trade, even though prices are marked in euros.

Transport
The city's Port of Ceuta receives high numbers of ferries each day from Algeciras in Andalusia in the south of Spain. The closest airport is Sania Ramel Airport in Morocco.

A single road border checkpoint to the south of Ceuta near Fnideq allows for cars and pedestrians to travel between Morocco and Ceuta. An additional border crossing for pedestrians exists between Benzú and Belyounech on the northern coast. The rest of the border is closed and inaccessible.

There is a bus service throughout the city, and while it does not pass into neighbouring Morocco, it services both frontier crossings.

Hospitals
The following hospitals are located within Ceuta:
 * University Hospital of Ceuta, established in 2010, 252 beds
 * Primary Care Emergency Services Jose Lafont
 * Ceuta Medical Centre
 * Spanish Military Hospital (500 beds in 1929, 2020 listed as a clinic)

Demographics
As of 2018, its population was 85,144. Due to its location, Ceuta is home to a mixed ethnic and religious population. The two main religious groups are Christians and Muslims. As of 2006 approximately 50% of the population was Christian and approximately 48% Muslim. As of a 2018 estimate, around 67.8% of the city's population were born in Ceuta.

Spanish is the primary and official language of the enclave. Moroccan Arabic (Darija) is widely spoken. In 2021, the Council of Europe demanded that Spain formally recognize the language by 2023.

Religion

Christianity has been present in Ceuta continuously from late antiquity, as evidenced by the ruins of a basilica in downtown Ceuta and accounts of the martyrdom of St. Daniel Fasanella and his Franciscans in 1227 during the Almohad Caliphate.

The town's Grand Mosque had been built over a Byzantine-era church. In 1415, the year of the city's conquest, the Portuguese converted the Grand Mosque into Ceuta Cathedral. The present form of the cathedral dates to refurbishments undertaken in the late 17th century, combining baroque and neoclassical elements. It was dedicated to StMary of the Assumption in 1726.

The Roman Catholic Diocese of Ceuta was established in 1417. It incorporated the suppressed Diocese of Tanger in 1570. The Diocese of Ceuta was a suffragan of Lisbon until 1675, when it became a suffragan of Seville. In 1851, Ceuta's administration was notionally merged into the Diocese of Cádiz and Ceuta as part of a concordat between Spain and the Holy See; the union was not actually accomplished, however, until 1879.

Small Jewish and Hindu minorities are also present in the city.

Migration
Like Melilla, Ceuta attracts African migrants who try to use it as an entry to Europe. As a result, the enclave is surrounded by double fences that are 6 m high, and hundreds of migrants congregate near the fences waiting for a chance to cross them. The fences are regularly stormed by migrants trying to claim asylum once they enter Ceuta.

Education
The University of Granada offers undergraduate programmes at their campus in Ceuta. Like all areas of Spain, Ceuta is also served by the National University of Distance Education (UNED).

While primary and secondary education are generally offered in Spanish only, a growing number of schools are entering the Bilingual Education Programme.

up to 1800

 * Qadi Ayyad (1083 in Ceuta – 1149) born in Ceuta, then belonging to the Almoravids was the great imam of that city
 * Muhammad al-Idrisi (1100 in Ceuta – 1165 in Ceuta) was a Muslim geographer, cartographer and Egyptologist. He lived in Palermo at the court of King Roger II of Sicily, known for the Tabula Rogeriana.
 * Abu al-Abbas as-Sabti (1129 in Ceuta – 1204 in Marrakesh) the main Wali of Marrakesh
 * Joseph ben Judah of Ceuta (c. 1160 – 1226) a Jewish physician and poet, and disciple of Moses Maimonides
 * Abu al-Abbas al-Azafi (1162 in Ceuta – 1236) a religious and legal scholar, member of the Banu al-Azafi who ruled Ceuta
 * Mohammed ibn Rushayd (1259 in Sabta – 1321) a judge, writer and scholar of Hadith
 * Álvaro of Braganza (1440–1504) a president of Council of Castile.
 * George Camocke (1666–1732) a Royal Navy captain and former admiral for Spain who was exiled to Ceuta to live out the last years of his life.
 * Don Fernando de Leyba (1734 in Ceuta – 1780) a Spanish officer who served as the third governor of Upper Louisiana from 1778 until his death.
 * Brigadier General Francisco Antonio García Carrasco Díaz (1742 in Ceuta – 1813 in Lima, Peru) a Spanish soldier and Royal Governor of Chile
 * Sebastián Kindelán y O'Regan (1757 in Ceuta – 1826 in Santiago de Cuba) a colonel in the Spanish Army who served as governor of East Florida 1812/1815, of Santo Domingo 1818/1821 and was provisional governor of Cuba 1822/1823
 * Isidro de Alaix Fábregas Count of Vergara and Viscount of Villarrobledo, (1790 in Ceuta – 1853 in Madrid) a Spanish general of the First Carlist War who backed Isabella II of Spain

since 1800

 * General Francisco Llano de la Encomienda (1879 in Ceuta – 1963 in Mexico City), a Spanish soldier. During the Spanish Civil War (1936–1939) he remained loyal to the Second Spanish Republic
 * General Antonio Escobar Huertas (1879 in Ceuta – executed 1940 in Barcelona), a Spanish military officer
 * África de las Heras Gavilán (1909 in Ceuta – 1988 in Moscow), a Spanish Communist, naturalized Soviet citizen, and KGB spy who went by the code name Patria
 * Eugenio Martín (born 1925 in Ceuta), a Spanish film director and screenwriter
 * Jacob Hassan, PhD (1936 in Ceuta – 2006 in Madrid), a Spanish philologist of Sephardic Jewish descent
 * Manuel Chaves González (born 1945 in Ceuta), a Spanish politician of the Spanish Socialist Workers' Party. He served as the Third Vice President of the Spanish Government from 2009 to 2011
 * Ramón Castellano de Torres (born 1947 in Ceuta), a Spanish artist, thought by some to be an expressionist painter
 * Ignacio Velázquez Rivera (born 1953), first Mayor-President of Melilla
 * Juan Jesús Vivas Lara (born 1953 in Ceuta), became the Mayor-President of Ceuta in Spain in 2001
 * Pedro Avilés Gutiérrez (born 1956 in Ceuta), a Spanish novelist from Madrid.
 * Eva María Isanta Foncuberta (born 1971 in Ceuta), a Spanish actress
 * Mohamed Taieb Ahmed (born 1975 in Ceuta), a Spanish-Moroccan drug lord responsible for trafficking hashish across the Strait of Gibraltar and into Spain.
 * Rakesh Narwani (born 1981 in Ceuta), a Spanish Filmmaker

Sport

 * Francisco Lesmes (1924–2005) and Rafael Lesmes (1926–2012), brothers and Spanish footballers.
 * José Martínez Sánchez (born 1945 in Ceuta), nicknamed Pirri, a retired Spanish footballer, mainly played for Real Madrid, appearing in 561 competitive games and scoring 172 goals
 * José Ramón López (born 1950), a sprint canoer, silver medallist at the 1976 Summer Olympics
 * Miguel Bernardo Bianquetti (born 1951 in Ceuta), known as Migueli, a Spanish retired footballer, 391 caps for FC Barcelona and 32 for Spain
 * Nayim (born 1966 in Ceuta), a retired Spanish footballer; he scored a last-minute goal for Real Zaragoza in the 1995 UEFA Cup Winners' Cup Final.
 * Lorena Miranda (born 1991 in Ceuta), a Spanish female water polo player, silver medallist at the 2012 Summer Olympics.
 * Anuar Tuhami (born 1995 in Ceuta), a Spanish-Moroccan footballer, played one game for Morocco

Twin towns and sister cities
Ceuta is twinned with:

 * Aci Catena, Italy
 * Algeciras, Spain (since 1997)
 * Buenos Aires, Argentina
 * Cádiz, Spain (since 2007)
 * Melilla, Spain
 * Santarém, Portugal

Dispute with Morocco
The Moroccan government has repeatedly called for Spain to transfer the sovereignty of Ceuta and Melilla, along with uninhabited islets such as the islands of Alhucemas, Vélez and Perejil to Morocco, with the Spanish refusal to do so serving as a major source of tension in Morocco–Spain relations. In Morocco, Ceuta is frequently referred to as the "occupied Sebtah", and the Moroccan government has argued that Ceuta, along with other Spanish territories in the region, are colonies. One of the major arguments used by Morocco in their attempts to acquire sovereignty over Ceuta refers to the geographical position of the city, as Ceuta is an exclave which is surrounded by Moroccan territory and the Mediterranean Sea and has no territorial continuity with the rest of Spain. This argument was originally developed by one of the founders of the Moroccan Istiqlal Party, Alal-El Faasi, who openly advocated for Morocco to invade and occupy Ceuta and other North African territories under Spanish rule. Spain, in line with the majority of governments in the rest of the world, has never recognized Morocco's claim over Ceuta. The official position of the Spanish government is that Ceuta is an integral part of Spain, and has been since the 16th century, centuries prior to Morocco's independence from Spain and France in 1956. The majority of Ceuta's population support continued Spanish sovereignty and are opposed to Moroccan control over the territory.

In 1986, Spain joined the North Atlantic Treaty Organization (NATO). However, Ceuta is not under NATO protection since Article 6 of the North Atlantic Treaty limits such coverage to Europe and North America and islands north of the Tropic of Cancer. However, French Algeria was explicitly included in the treaty upon France's entry. Legal experts have claimed that other articles of the treaty could cover Spanish territories in North Africa but this interpretation has not been tested in practice. During the 2022 Madrid summit, the issue of the protection of Ceuta was raised by Spain, with NATO Secretary General Jens Stoltenberg stating: "On which territories NATO protects and Ceuta and Melilla, NATO is there to protect all Allies against any threats. At the end of the day, it will always be a political decision to invoke Article 5, but rest assured NATO is there to protect and defend all Allies". On 21 December 2020, following statements made by Moroccan Prime Minister Saadeddine Othmani that Ceuta is "Moroccan as the Sahara", the Spanish government summoned the Moroccan ambassador, Karima Benyaich, to convey that Spain expects all its partners to respect the sovereignty and territorial integrity of its territory in Africa and asked for an explanation for Othmani's words.

title: Ceuta


text:
Cleopatra (disambiguation)

Cleopatra (69–30 BC) was the last active Ptolemaic ruler of Egypt before it became a Roman province.

Cleopatra may also refer to:

Given name

 * Cleopatra (given name), a list of people and fictional characters
 * Cleopatra (Greek singer) (born 1963), who represented Greece in the 1992 Eurovision Song Contest
 * Cleopatra (Greek myth), a list of mythological figures

Film

 * Cleopatra (1912 film), an American silent film
 * Cleopatra (1917 film), an American silent film
 * Cleopatra (1928 film), an American silent short film
 * Cleopatra (1934 film), an American film by Cecil B. DeMille
 * Cleopatra (1963 film), an American film by Joseph L. Mankiewicz starring Elizabeth Taylor and Richard Burton
 * Cleopatra (1970 film), a Japanese anime film
 * Cleopatra (2003 film), an Argentine film
 * Cleopatra (2005 film), an Indian Tamil-language film
 * Cleopatra (2007 film), a Brazilian film by Júlio Bressane
 * Cleopatra (2013 film), an Indian Malayalam-language film
 * Foxxy Cleopatra, a major character in the 2002 film Austin Powers in Goldmember

Literature

 * Cleopatra (Rider Haggard novel) (1889)
 * Cleopatra (Gardner novel), a 1962 novel by Jeffrey K. Gardner
 * La Cleopatra (poem), an epic poem by Girolamo Graziani
 * the title character of Cleopatra in Space, an American graphic novel series for children by Mike Maihack

Classical music

 * Cleopatra (Cimarosa), a 1789 opera seria by Domenico Cimarosa
 * Cleopatra (Rossi), an 1876 opera by Lauro Rossi
 * Cleopatra, an opera by Johann Mattheson
 * Cleopatra, a composition by Luigi Mancinelli
 * Cleopatra, a symphonic poem by George Whitefield Chadwick

Popular music

 * Cleopatra Records, an American record label
 * Cleopatra (group), a British girl group

Albums

 * Cleopatra (album), a 2016 album by The Lumineers
 * Cleopatra (1963 soundtrack), a soundtrack by Alex North
 * Cleopatra, a 2004 album by Isabel Bayrakdarian
 * Handel: Cleopatra, a 2011 album by Natalie Dessay

Songs

 * "Cleopatra" (Frankie Avalon song) (1963)
 * "Cleopatra" (Jerome Kern song) (1917)
 * "Cleopatra" (Samira Efendi song), Azerbaijan's 2020 Eurovision song submission.
 * "Cleopatra" (The Lumineers song) (2016)
 * "Cleopatra" (Weezer song) (2014)
 * "Cleopatra (I've Got to Get You Off My Mind)", a song by The Tennors
 * "Cleopatra", a song by Adam and the Ants from their 1979 album Dirk Wears White Sox
 * "Cleopatra", a song by Nico Fidenco
 * "Cleopatra", a song by David Vendetta
 * "Cleopatra", a song by Train from AM Gold (album), 2022

Paintings

 * Cleopatra (Artemisia Gentileschi, Ferrara), by Artemisia Gentileschi, c. 1620
 * Cleopatra (Artemisia Gentileschi, Milan), by Artemisia Gentileschi, 1613 or 1621–1622
 * Cleopatra (Artemisia Gentileschi, Rome), by Artemisia Gentileschi, c. 1633-5

Television

 * Cleopatra (miniseries), a 1999 American miniseries produced by Hallmark Entertainment
 * Cleopatra 2525, an American science fiction television series
 * The Cleopatras, a 1983 British series

Places

 * Cleopatra (neighborhood), a neighborhood of Alexandria, Egypt
 * Cleopatra, Kentucky, United States, an unincorporated community
 * Cleopatra, Missouri, United States, an unincorporated community
 * Cleopatra (crater), an impact crater on Venus

Plants and animals

 * Cleopatra (horse), an American racehorse
 * Cleopatra (gastropod), a genus of freshwater snails
 * Gonepteryx cleopatra or cleopatra, a species of butterfly
 * Neoguillauminia cleopatra, a species of tree from New Caledonia

Ships

 * HMS Cleopatra, various Royal Navy ships
 * Cleopatra, an East India Company paddle frigate built in 1839 and sunk by a tropical cyclone in 1847
 * Cleopatra (cylinder ship), a vessel constructed to convey Cleopatra's Needle from Alexandria to London in 1877
 * SS Mohegan, originally named Cleopatra, a mixed passenger liner and animal carrier which sank in 1898
 * SS United Victory, a World War II Victory cargo ship renamed Cleopatra in 1956

Other uses

 * Cleopatra (cigarette), an Egyptian brand

title: Cleopatra (disambiguation)


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Carcinogen

A carcinogen is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruses and bacteria. Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation. This occurs when the cell's DNA repair processes fail to identify DNA damage allowing the defect to be passed down to daughter cells. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.

The specific mechanisms for carcinogenic activity is unique to each agent and cell type. Carcinogens can be broadly categorized, however, as activation-dependent and activation-independent which relate to the agent's ability to engage directly with DNA. Activation-dependent agents are relatively inert in their original form, but are bioactivated in the body into metabolites or intermediaries capable of damaging human DNA. These are also known as "indirect-acting" carcinogens. Examples of activation-dependent carcinogens include polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, and mycotoxins. Activation-independent carcinogens, or "direct-acting" carcinogens, are those that are capable of directly damaging DNA without any modification to their molecular structure. These agents typically include electrophilic groups that react readily with the net negative charge of DNA molecules. Examples of activation-independent carcinogens include ultraviolet light, ionizing radiation and alkylating agents.

The time from exposure to a carcinogen to the development of cancer is known as the latency period. For most solid tumors in humans the latency period is between 10 and 40 years depending on cancer type. For blood cancers, the latency period may be as short as two. Due to prolonged latency periods identification of carcinogens can be challenging.

A number of organizations review and evaluate the cumulative scientific evidence regarding the potential carcinogenicity of specific substances. Foremost among these is the International Agency for Research on Cancer (IARC). IARC routinely publishes monographs in which specific substances are evaluated for their potential carcinogenicity to humans and subsequently categorized into one of four groupings: Group 1: Carcinogenic to humans, Group 2A: Probably carcinogenic to humans, Group 2B: Possibly carcinogenic to humans and Group 3: Not classifiable as to its carcinogenicity to humans. Other organizations that evaluate the carcinogenicity of substances include the National Toxicology Program of the US Public Health Service, NIOSH, the American Conference of Governmental Industrial Hygienists and others.

There are numerous sources of exposures to carcinogens including ultraviolet radiation from the sun, radon gas emitted in residential basements, environmental contaminants such as chlordecone, cigarette smoke and ingestion of some types of foods such as alcohol and processed meats. Occupational exposures represent a major source of carcinogens with an estimated 666,000 annual fatalities worldwide attributable to work related cancers. According to NIOSH, 3-6% of cancers worldwide are due to occupational exposures. Well established occupational carcinogens include vinyl chloride and hemangiosarcoma of the liver, benzene and leukemia, aniline dyes and bladder cancer, asbestos and mesothelioma, polycyclic aromatic hydrocarbons and scrotal cancer among chimney sweeps to name a few.

Ionizing Radiation
CERCLA identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, gamma, or neutron and the radioactive strength), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenicity of radiation depends on the type of radiation, type of exposure, and penetration. For example, alpha radiation has low penetration and is not a hazard outside the body, but emitters are carcinogenic when inhaled or ingested. For example, Thorotrast, a (incidentally radioactive) suspension previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles. Low-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and cancer.

Non-ionizing radiation
Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the electromagnetic spectrum including radio waves, microwaves, infrared radiation and visible light are thought not to be, because they have insufficient energy to break chemical bonds. Evidence for carcinogenic effects of non-ionizing radiation is generally inconclusive, though there are some documented cases of radar technicians with prolonged high exposure experiencing significantly higher cancer incidence.

Higher-energy radiation, including ultraviolet radiation (present in sunlight) generally is carcinogenic, if received in sufficient doses. For most people, ultraviolet radiations from sunlight is the most common cause of skin cancer. In Australia, where people with pale skin are often exposed to strong sunlight, melanoma is the most common cancer diagnosed in people aged 15–44 years.

Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic. In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.

Alcohol
Alcohol is a carcinogen of the head and neck, esophagus, liver, colon and rectum, and breast. It has a synergistic effect with tobacco smoke in the development of head and neck cancers. In the United states approximately 6% of cancers and 4% of cancer deaths are attributable to alcohol use.

Processed Meats
Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may produce carcinogens. For example, nitrites used as food preservatives in cured meat such as bacon have also been noted as being carcinogenic with demographic links, but not causation, to colon cancer.

Meats cooked at high temperatures
Cooking food at high temperatures, for example grilling or barbecuing meats, may also lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzo[a]pyrene). Charring of food looks like coking and tobacco pyrolysis, and produces carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2–3 minutes before grilling shortens the time on the hot pan, and removes heterocyclic amine (HCA) precursors, which can help minimize the formation of these carcinogens.

Acrylamide in foods
Frying, grilling or broiling food at high temperatures, especially starchy foods, until a toasted crust is formed generates acrylamides. This discovery in 2002 led to international health concerns. Subsequent research has however found that it is not likely that the acrylamides in burnt or well-cooked food cause cancer in humans; Cancer Research UK categorizes the idea that burnt food causes cancer as a "myth".

Biologic Agents
Several biologic agents are known carcinogens.

Aflatoxin B1, a toxin produced by the fungus Aspergillus flavus which is a common contaminant of stored grains and nuts is a known cause of hepatocellular cancer. The bacteria H. Pylori is known to cause stomach cancer and MALT lymphoma. Hepatitis B and C are associated with the development of hepatocellular cancer. HPV is the primary cause of cervical cancer.

Cigarette smoke
Tobacco smoke contains at least 70 known carcinogens and is implicated in the development of numerous types of cancers including cancers of the lung, larynx, esophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon, rectum and blood. Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons (PAH, such as benzo(a)pyrene), benzene, and nitrosamine.

Occupational carcinogens
Given that populations of workers are more likely to have consistent, often high level exposures to chemicals rarely encountered in normal life, much of the evidence for the carcinogenicity of specific agents is derived from studies of workers.

Selected carcinogens

Others

 * Gasoline (contains aromatics)
 * Lead and its compounds
 * Alkylating antineoplastic agents (e.g., mechlorethamine)
 * Styrene
 * Other alkylating agents (e.g., dimethyl sulfate)
 * Ultraviolet radiation from the sun and UV lamps
 * Other ionizing radiation (X-rays, gamma rays, etc.)
 * Low refining or unrefined mineral oils

Mechanisms of carcinogenicity
Carcinogens can be classified as genotoxic or nongenotoxic. Genotoxins cause irreversible genetic damage or mutations by binding to DNA. Genotoxins include chemical agents like N-nitroso-N-methylurea (NMU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA.

Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.

International Agency for Research on Cancer
The International Agency for Research on Cancer (IARC) is an intergovernmental agency established in 1965, which forms part of the World Health Organization of the United Nations. It is based in Lyon, France. Since 1971 it has published a series of Monographs on the Evaluation                         of Carcinogenic Risks to Humans that have been highly influential in the classification of possible carcinogens.
 * Group 1: the agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
 * Group 2A: the agent (mixture) is most likely (product more likely to be) carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
 * Group 2B: the agent (mixture) is possibly (chance of product being) carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
 * Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
 * Group 4: the agent (mixture) is most likely not carcinogenic to humans.

Globally Harmonized System
The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a United Nations initiative to attempt to harmonize the different systems of assessing chemical risk which currently exist (as of March 2009) around the world. It classifies carcinogens into two categories, of which the first may be divided again into subcategories if so desired by the competent regulatory authority:
 * Category 1: known or presumed to have carcinogenic potential for humans
 * Category 1A: the assessment is based primarily on human evidence
 * Category 1B: the assessment is based primarily on animal evidence
 * Category 2: suspected human carcinogens

U.S. National Toxicology Program
The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens. As of June 2011, the latest edition was the 12th report (2011). It classifies carcinogens into two groups:
 * Known to be a human carcinogen
 * Reasonably anticipated being a human carcinogen

American Conference of Governmental Industrial Hygienists
The American Conference of Governmental Industrial Hygienists (ACGIH) is a private organization best known for its publication of threshold limit values (TLVs) for occupational exposure and monographs on workplace chemical hazards. It assesses carcinogenicity as part of a wider assessment of the occupational hazards of chemicals.
 * Group A1: Confirmed human carcinogen
 * Group A2: Suspected human carcinogen
 * Group A3: Confirmed animal carcinogen with unknown relevance to humans
 * Group A4: Not classifiable as a human carcinogen
 * Group A5: Not suspected as a human carcinogen

European Union
The European Union classification of carcinogens is contained in the Regulation (EC) No 1272/2008. It consists of three categories:

 * Category 1A: Carcinogenic
 * Category 1B: May cause cancer
 * Category 2: Suspected of causing cancer

The former European Union classification of carcinogens was contained in the Dangerous Substances Directive and the Dangerous Preparations Directive. It also consisted of three categories: This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions.
 * Category 1: Substances known to be carcinogenic to humans.
 * Category 2: Substances which should be regarded as if they are carcinogenic to humans.
 * Category 3: Substances which cause concern for humans, owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment.

Safe Work Australia
Under a previous name, the NOHSC, in 1999 Safe Work Australia published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)]. Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories:
 * Category 1: Substances known to be carcinogenic to humans.
 * Category 2: Substances that should be regarded as if they were carcinogenic to humans.
 * Category 3: Substances that have possible carcinogenic effects in humans but about which there is insufficient information to make an assessment.

Major carcinogens implicated in the four most common cancers worldwide
In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described. These four cancers are lung, breast, colon, and stomach cancers. Together they account for about 41% of worldwide cancer incidence and 42% of cancer deaths (for more detailed information on the carcinogens implicated in these and other cancers, see references ).

Lung cancer
Lung cancer (pulmonary carcinoma) is the most common cancer in the world, both in terms of cases (1.6 million cases; 12.7% of total cancer cases) and deaths (1.4 million deaths; 18.2% of total cancer deaths). Lung cancer is largely caused by tobacco smoke. Risk estimates for lung cancer in the United States indicate that tobacco smoke is responsible for 90% of lung cancers. Other factors are implicated in lung cancer, and these factors can interact synergistically with smoking so that total attributable risk adds up to more than 100%. These factors include occupational exposure to carcinogens (about 9-15%), radon (10%) and outdoor air pollution (1-2%). Tobacco smoke is a complex mixture of more than 5,300 identified chemicals. The most important carcinogens in tobacco smoke have been determined by a "Margin of Exposure" approach. Using this approach, the most important tumorigenic compounds in tobacco smoke were, in order of importance, acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, cadmium, acetaldehyde, ethylene oxide, and isoprene. Most of these compounds cause DNA damage by forming DNA adducts or by inducing other alterations in DNA. DNA damages are subject to error-prone DNA repair or can cause replication errors. Such errors in repair or replication can result in mutations in tumor suppressor genes or oncogenes leading to cancer.

Breast cancer
Breast cancer is the second most common cancer [(1.4 million cases, 10.9%), but ranks 5th as cause of death (458,000, 6.1%)]. Increased risk of breast cancer is associated with persistently elevated blood levels of estrogen. Estrogen appears to contribute to breast carcinogenesis by three processes; (1) the metabolism of estrogen to genotoxic, mutagenic carcinogens, (2) the stimulation of tissue growth, and (3) the repression of phase II detoxification enzymes that metabolize ROS leading to increased oxidative DNA damage. The major estrogen in humans, estradiol, can be metabolized to quinone derivatives that form adducts with DNA. These derivatives can cause depurination, the removal of bases from the phosphodiester backbone of DNA, followed by inaccurate repair or replication of the apurinic site leading to mutation and eventually cancer. This genotoxic mechanism may interact in synergy with estrogen receptor-mediated, persistent cell proliferation to ultimately cause breast cancer. Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk.

Consumption of alcohol has also been linked to an increased risk for breast cancer.

Colon cancer
Colorectal cancer is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)]. Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States. In addition, substantial evidence implicates bile acids as an important factor in colon cancer. Twelve studies (summarized in Bernstein et al. ) indicate that the bile acids deoxycholic acid (DCA) or lithocholic acid (LCA) induce production of DNA-damaging reactive oxygen species or reactive nitrogen species in human or animal colon cells. Furthermore, 14 studies showed that DCA and LCA induce DNA damage in colon cells. Also 27 studies reported that bile acids cause programmed cell death (apoptosis). Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis. Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer. Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer. Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids. When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months. Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer.

Stomach cancer
Stomach cancer is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)]. Helicobacter pylori infection is the main causative factor in stomach cancer. Chronic gastritis (inflammation) caused by H. pylori is often long-standing if not treated. Infection of gastric epithelial cells with H. pylori results in increased production of reactive oxygen species (ROS). ROS cause oxidative DNA damage including the major base alteration 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG resulting from ROS is increased in chronic gastritis. The altered DNA base can cause errors during DNA replication that have mutagenic and carcinogenic potential. Thus H. pylori-induced ROS appear to be the major carcinogens in stomach cancer because they cause oxidative DNA damage leading to carcinogenic mutations. Diet is thought to be a contributing factor in stomach cancer - in Japan where very salty pickled foods are popular, the incidence of stomach cancer is high. Preserved meat such as bacon, sausages, and ham increases the risk while a diet rich in fresh fruit, vegetables, peas, beans, grains, nuts, seeds, herbs, and spices will reduce the risk. The risk also increases with age.

title: Carcinogen