Editing Mutagen (section)

==Discovery==
The first mutagens to be identified were [[carcinogen]]s, substances that were shown to be linked to [[cancer]]. [[Tumor]]s were described more than 2,000 years before the discovery of [[chromosome]]s and [[DNA]]; in 500 B.C., the Greek [[physician]] [[Hippocrates]] named tumors resembling a crab ''karkinos'' (from which the word "cancer" is derived via Latin), meaning crab.<ref>{{cite journal | vauthors = Papavramidou N, Papavramidis T, Demetriou T | title = Ancient Greek and Greco-Roman methods in modern surgical treatment of cancer | journal = Annals of Surgical Oncology | volume = 17 | issue = 3 | pages = 665–7 | date = March 2010 | pmid = 20049643 | pmc = 2820670 | doi = 10.1245/s10434-009-0886-6 }}</ref> In 1567, Swiss physician [[Paracelsus]] suggested that an unidentified substance in mined ore (identified as [[radon]] gas in modern times) caused a wasting disease in miners,<ref name="Luch Nature and nurture">{{cite journal |last1=Luch |first1=Andreas |title=Nature and nurture – lessons from chemical carcinogenesis |journal=Nature Reviews Cancer |date=February 2005 |volume=5 |issue=2 |pages=113–125 |doi=10.1038/nrc1546 |pmid=15660110 }}</ref> and in England, in 1761, [[John Hill (author)|John Hill]] made the first direct link of cancer to chemical substances by noting that excessive use of [[snuff (tobacco)|snuff]] may cause nasal cancer.<ref>{{Cite book|url=http://resource.nlm.nih.gov/2166041R|title=Cautions against the immoderate use of snuff: founded on the known qualities of the tobacco plant: and the effects it must produce when this way taken into the body: and enforced by instances of persons who have perished miserably of diseases, occasioned, or rendered incurable by its use|last=Hill|first=John|publisher=Printed for Baldwin R and Jackson J|year=1761|location=London|name-list-style=vanc}}</ref> In 1775, Sir [[Percivall Pott]] wrote a paper on the high incidence of scrotal cancer in [[chimney sweep]]s, and suggested chimney [[soot]] as the cause of scrotal cancer.<ref>{{cite journal | vauthors = Brown JR, Thornton JL | title = Percivall Pott (1714-1788) and chimney sweepers' cancer of the scrotum | journal = British Journal of Industrial Medicine | volume = 14 | issue = 1 | pages = 68–70 | date = January 1957 | pmid = 13396156 | pmc = 1037746 | doi = 10.1136/oem.14.1.68 }}</ref> In 1915, Yamagawa and Ichikawa showed that repeated application of coal tar to rabbit's ears produced malignant cancer.<ref>{{cite journal|vauthors=Yamagawa K, Ichikawa K|year=1915|title=Experimentelle Studie über die Pathogenese der Epithelialgeschwülste|journal=Mitteilungen aus der Medizinischen Fakultät der Kaiserlichen Universität zu Tokyo|volume=15|pages=295–344|doi=10.11501/1675887}}</ref> Subsequently, in the 1930s the carcinogen component in coal tar was identified as a [[Polycyclic aromatic hydrocarbon|polyaromatic hydrocarbon]] (PAH), [[benzo(a)pyrene|benzo[a]pyrene]].<ref name="Luch Nature and nurture"/><ref>{{cite journal|vauthors=Cook JW, Hewett CL, Hieger I|year=1933|title=The isolation of a cancer-producing hydrocarbon from coal tar|journal=[[Journal of the Chemical Society|J. Chem. Soc.]]|volume=24|pages=395–405|doi=10.1039/JR9330000395|df=dmy-all}}</ref> Polyaromatic hydrocarbons are also present in soot, which was suggested to be a causative agent of cancer over 150 years earlier.

The association of exposure to radiation and cancer had been observed as early as 1902, six years after the discovery of X-ray by [[Wilhelm Röntgen]] and radioactivity by [[Henri Becquerel]].<ref>{{cite journal|vauthors=Kathren RL|date=Dec 2002|title=Historical Development of the Linear Nonthreshold Dose-Response Model as Applied to Radiation|url=https://scholars.unh.edu/unh_lr/vol1/iss1/5/|journal=University of New Hampshire Law Review|volume=1|issue=1}}</ref> [[Georgii Nadson]] and German Filippov were the first who created fungi mutants under [[ionizing radiation]] in 1925.<ref>{{Cite news|url=https://scfh.ru/en/papers/quot-russian-trail-quot-in-the-discovery-of-dna-structure/|title="Russian Trail" in the Discovery of DNA Structure|date=2004|work=SCIENCE First Hand|archive-url=https://web.archive.org/web/20170818090349/https://scfh.ru/en/papers/quot-russian-trail-quot-in-the-discovery-of-dna-structure/|archive-date=18 August 2017|url-status=live|publisher=INFOLIO|issue=N2|volume=3}}</ref><ref>{{cite book|title=Bericht über das Jahr 1960|vauthors=Böhme H|publisher=Springer Verlag|year=1961|isbn=978-3-642-94811-4|veditors=Bünning E, Gäumann E|volume=23|location=Berlin|pages=502–509|language=de|chapter=Angewandte Mikrobiologie|doi=10.1007/978-3-642-94810-7_40|quote=Bereits kurz nach der Entdeckung der Möglichkeit einer Auslösung von Mutationen durch ionisierende Strahlen (Nadson u. Filippov 1925, 1928; Muller 1927)}}</ref> The mutagenic property of mutagens was first demonstrated in 1927, when [[Hermann Joseph Muller|Hermann Muller]] discovered that [[x-ray]]s can cause genetic mutations in [[Drosophila melanogaster|fruit flies]], producing [[phenotype|phenotypic]] mutants as well as observable changes to the chromosomes,<ref name="Calabrese Nobel lecture">{{cite journal |last1=Calabrese |first1=Edward J. |title=Muller's Nobel lecture on dose–response for ionizing radiation: ideology or science? |journal=Archives of Toxicology |date=December 2011 |volume=85 |issue=12 |pages=1495–1498 |doi=10.1007/s00204-011-0728-8 |pmid=21717110 |bibcode=2011ArTox..85.1495C }}</ref><ref>{{cite journal |last1=Muller |first1=H. J. |title=Artificial Transmutation of the Gene |journal=Science |date=22 July 1927 |volume=66 |issue=1699 |pages=84–87 |doi=10.1126/science.66.1699.84 |pmid=17802387 |bibcode=1927Sci....66...84M }}</ref> visible due to the presence of enlarged [[Polytene chromosome|"polytene" chromosomes]] in fruit fly salivary glands.<ref>{{cite book|title=Introduction to Genetic Analysis|last1=Griffiths|first1=Anthony J. F.|last2=Wessler|first2=Susan R.|last3=Carroll|first3=Sean B.|last4=Doebley|first4=John|date=2012|publisher=W. H. Freeman|isbn=978-1-4292-7634-4|edition=10th|page=255|name-list-style=vanc}}</ref> His collaborator [[Edgar Altenburg]] also demonstrated the mutational effect of UV radiation in 1928.<ref>{{Cite journal|vauthors=Altenburg E|date=1928|title=The Limit of Radiation Frequency Effective in Producing Mutations|journal=[[The American Naturalist|Am. Nat.]]|volume=62|issue=683|pages=540–545|jstor=2457052|doi=10.1086/280230|bibcode=1928ANat...62..540A |s2cid=83653780}}</ref> Muller went on to use x-rays to create [[Drosophila]] mutants that he used in his studies of [[genetics]].<ref>{{cite journal | vauthors = Crow JF, Abrahamson S | title = Seventy years ago: mutation becomes experimental | journal = Genetics | volume = 147 | issue = 4 | pages = 1491–6 | date = December 1997 | doi = 10.1093/genetics/147.4.1491 | pmid = 9409815 | pmc = 1208325 }}</ref> He also found that X-rays not only mutate [[gene]]s in fruit flies,<ref name="Calabrese Nobel lecture"/> but also have effects on the genetic makeup of humans.<ref>{{cite book|title=Biology|vauthors=Campbell NA, Reece JB|publisher=Pearson Education, Inc|year=2005|isbn=978-0-8053-7146-8|edition=7th|location=San Francisco, CA}}</ref>{{better source needed|date=July 2017}} Similar work by [[Lewis Stadler]] also showed the mutational effect of X-rays on barley in 1928,<ref>{{cite journal | vauthors = Stadler LJ | title = Mutations in Barley Induced by X-Rays and Radium | journal = Science | volume = 68 | issue = 1756 | pages = 186–7 | date = August 1928 | pmid = 17774921 | doi = 10.1126/science.68.1756.186 | bibcode = 1928Sci....68..186S }}</ref> and [[ultraviolet]] (UV) radiation on maize in 1936.<ref name="stadler">{{cite journal | vauthors = Stadler LJ, Sprague GF | title = Genetic Effects of Ultra-Violet Radiation in Maize: I. Unfiltered Radiation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 22 | issue = 10 | pages = 572–8 | date = October 1936 | pmid = 16588111 | pmc = 1076819 | doi = 10.1073/pnas.22.10.572 | bibcode = 1936PNAS...22..572S | author-link1 = Lewis Stadler | doi-access = free }}</ref> The effect of sunlight had previously been noted in the nineteenth century where rural outdoor workers and sailors were found to be more prone to skin cancer.<ref>{{cite journal |last1=Hockberger |first1=Philip E. |title=A History of Ultraviolet Photobiology for Humans, Animals and Microorganisms |journal=Photochemistry and Photobiology |date=May 2007 |volume=76 |issue=6 |pages=561–579 |doi=10.1562/0031-8655(2002)0760561AHOUPF2.0.CO2 }}</ref>

[[Chemical mutagen]]s were not demonstrated to cause mutation until the 1940s, when [[Charlotte Auerbach]] and [[J. M. Robson]] found that [[mustard gas]] can cause [[mutation]]s in fruit flies.<ref>{{cite journal | vauthors = Auerbach C, Robson JM, Carr JG | title = The Chemical Production of Mutations | journal = Science | volume = 105 | issue = 2723 | pages = 243–7 | date = March 1947 | pmid = 17769478 | doi = 10.1126/science.105.2723.243 | bibcode = 1947Sci...105..243A | author-link = Charlotte Auerbach }}</ref> A large number of chemical mutagens have since been identified, especially after the development of the [[Ames test]] in the 1970s by [[Bruce Ames]] that screens for mutagens and allows for preliminary identification of carcinogens.<ref>{{cite journal | vauthors = Ames BN, Lee FD, Durston WE | title = An improved bacterial test system for the detection and classification of mutagens and carcinogens | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 70 | issue = 3 | pages = 782–6 | date = March 1973 | pmid = 4577135 | pmc = 433358 | doi = 10.1073/pnas.70.3.782 | bibcode = 1973PNAS...70..782A | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ames BN | title = Identifying environmental chemicals causing mutations and cancer | journal = Science | volume = 204 | issue = 4393 | pages = 587–93 | date = May 1979 | pmid = 373122 | doi = 10.1126/science.373122 | bibcode = 1979Sci...204..587A | jstor = 1748159 | author-link = Bruce Ames }}</ref> Early studies by Ames showed around 90% of known carcinogens can be identified in Ames test as mutagenic (later studies however gave lower figures),<ref>{{cite journal | vauthors = McCann J, Choi E, Yamasaki E, Ames BN | title = Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 12 | pages = 5135–9 | date = December 1975 | pmid = 1061098 | pmc = 388891 | doi = 10.1073/pnas.72.12.5135 | bibcode = 1975PNAS...72.5135M | display-authors = 3 | doi-access = free }}</ref><ref>{{cite journal |last1=McCann |first1=Joyce |last2=Swirsky Gold |first2=Lois |last3=Horn |first3=Laura |last4=McGill |first4=R. |last5=Graedel |first5=T.E. |last6=Kaldor |first6=John |title=Statistical analysis of Salmonella test data and comparison to results of animal cancer tests |journal=Mutation Research/Genetic Toxicology |date=January 1988 |volume=205 |issue=1–4 |pages=183–195 |doi=10.1016/0165-1218(88)90017-1 |pmid=3285186 }}</ref><ref name="dunkel"/> and ~80% of the mutagens identified through Ames test may also be carcinogens.<ref name="dunkel">{{cite journal | vauthors = Dunkel VC, Zeiger E, Brusick D, McCoy E, McGregor D, Mortelmans K, Rosenkranz HS, Simmon VF | title = Reproducibility of microbial mutagenicity assays: II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli | journal = Environmental Mutagenesis | volume = 7 Suppl 5 | issue = suppl. 5 | pages = 1–248 | year = 1985 | pmid = 3905369 | display-authors = 3 | doi = 10.1002/em.2860070902 }}</ref><ref>{{cite journal | vauthors = Benigni R, Bossa C | title = Alternative strategies for carcinogenicity assessment: an efficient and simplified approach based on in vitro mutagenicity and cell transformation assays | journal = Mutagenesis | volume = 26 | issue = 3 | pages = 455–60 | date = May 2011 | pmid = 21398403 | doi = 10.1093/mutage/ger004 | doi-access = free }}</ref>