Editing Mutagenesis (section)

==History==
DNA may be modified, either naturally or artificially, by a number of physical, chemical and biological agents, resulting in [[mutation]]s. [[Hermann Joseph Muller|Hermann Muller]] found that "high temperatures" have the ability to mutate genes in the early 1920s,<ref>{{cite web |url=https://embryo.asu.edu/pages/hermann-joseph-mullers-study-x-rays-mutagen-1926-1927 |title=Hermann Joseph Muller's Study of X-rays as a Mutagen, (1926-1927) |author= Kevin M. Gleason Published: 2017-03-07 }}</ref> and in 1927, demonstrated a causal link to mutation upon experimenting with an [[x-ray machine]], noting [[phylogenetic]] changes when irradiating [[Drosophila melanogaster|fruit flies]] with relatively [[dose rate|high dose]] of [[X-ray]]s.<ref>{{cite web|url=http://www.genomenewsnetwork.org/resources/timeline/1927_Muller.php |title=Genetics and Genomics Timeline 1927 Hermann J. Muller (1890-1967) demonstrates that X rays can induce mutations }}</ref><ref>{{Cite journal 
| last1 = Muller | first1 = H. J. 
| title = Artificial Transmutation of the Gene 
| url = http://www.esp.org/foundations/genetics/classical/holdings/m/hjm-1927a.pdf
| doi = 10.1126/science.66.1699.84 
| journal = Science 
| volume = 66 
| issue = 1699 
| pages = 84–87 
| year = 1927 
| pmid = 17802387 
| bibcode = 1927Sci....66...84M 
}}</ref> Muller observed a number of chromosome rearrangements in his experiments, and suggested mutation as a cause of cancer.<ref>{{Cite journal 
| last1 = Crow | first1 = J. F. 
| last2 = Abrahamson | first2 = S. 
| title = Seventy Years Ago: Mutation Becomes Experimental 
| journal = Genetics 
| volume = 147 
| issue = 4 
| pages = 1491–1496 
| year = 1997 
| doi = 10.1093/genetics/147.4.1491 
| pmid = 9409815 
| pmc = 1208325
}}</ref><ref>{{Cite journal| author = Calabrese, E. J.| title = Muller's Nobel lecture on dose–response for ionizing radiation:ideology or science?| date = 30 June 2011| url = http://users.physics.harvard.edu/~wilson/freshman_seminar/Radiation/Calabrese-Muller-1-1.pdf| access-date = 30 December 2011| doi = 10.1007/s00204-011-0728-8| journal = Archives of Toxicology| volume = 85| issue = 4| pages = 1495–1498| pmid = 21717110| s2cid = 4708210| archive-date = 2 August 2017| archive-url = https://web.archive.org/web/20170802001406/http://users.physics.harvard.edu/~wilson/freshman_seminar/Radiation/Calabrese-Muller-1-1.pdf| url-status = dead}}</ref> 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 the discovery of radioactivity by [[Henri Becquerel]].<ref>{{cite journal |url= https://scholars.unh.edu/unh_lr/vol1/iss1/5/|journal=University of New Hampshire Law Review |volume= 1|issue= 1|date=December 2002 |title=Historical Development of the Linear Nonthreshold Dose-Response Model as Applied to Radiation|author=Ronald L. Kathren }}</ref> [[Lewis Stadler]], Muller's contemporary, also showed the effect of X-rays on mutations in barley in 1928, and of [[ultraviolet]] (UV) radiation on maize in 1936.<ref name="stadler">{{cite journal | last = Stadler| first = L. J. | author-link = Lewis Stadler |author2=G. F. Sprague | title = Genetic Effects of Ultra-Violet Radiation in Maize. I. Unfiltered Radiation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 22 | issue = 10 | pages = 572–8 | date = 1936-10-15 | url = http://www.pnas.org/cgi/reprint/22/10/579.pdf | doi = 10.1073/pnas.22.10.572| access-date = 2007-10-11 | pmid = 16588111 | pmc = 1076819 | bibcode = 1936PNAS...22..572S | doi-access = free }}</ref> In 1940s, [[Charlotte Auerbach]] and [[J. M. Robson]] found that [[mustard gas]] can also cause mutations in fruit flies.<ref>{{cite journal |author-link=Charlotte Auerbach |first1=C. |last1=Auerbach |first2=J.M. |last2=Robson |first3=J.G. |last3=Carr |title=Chemical Production of Mutations |journal=Science |volume=105 |issue=2723 |pages=243–7 |date=March 1947 |doi=10.1126/science.105.2723.243  |pmid=17769478 |bibcode=1947Sci...105..243A}}</ref>

While changes to the chromosome caused by X-ray and mustard gas were readily observable to early researchers, other changes to the DNA induced by other mutagens were not so easily observable; the mechanism by which they occur may be complex, and take longer to unravel. For example, soot was suggested to be a cause of cancer as early as 1775,<ref>{{Cite journal 
| last1 = Brown | first1 = J. R. 
| last2 = Thornton | first2 = J. L. 
| 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 
| year = 1957 
| pmid = 13396156 
| pmc = 1037746
 | doi=10.1136/oem.14.1.68
}}</ref> and coal tar was demonstrated to cause cancer in 1915.<ref>{{cite journal |vauthors=Yamagawa K, Ichikawa K |title=Experimentelle Studie ueber die Pathogenese der Epithel geschwuelste |journal=Mitteilungen aus der Medizinischen Fakultät der Kaiserlichen Universität zu Tokyo |volume=15 |pages=295–344 |year=1915 }}</ref> The chemicals involved in both were later shown to be [[polycyclic aromatic hydrocarbon]]s (PAH).<ref>{{cite web |first=Andreas |last=Luch |title=Nature and Nurture — Lessons from Chemical Carcinogenesis: Chemical Carcinogens — From Past to Present |date=2005 |publisher=Medscape |url=http://www.medscape.com/viewarticle/499098_2}}</ref> PAHs by themselves are not carcinogenic, and it was proposed in 1950 that the carcinogenic forms of PAHs are the oxides produced as metabolites from cellular processes.<ref>{{cite journal |author=Boyland E |title=The biological significance of metabolism of polycyclic compounds |journal=Biochemical Society Symposium |volume=5 |pages=40–54 |year=1950 |issn=0067-8694 |oclc=216723160 |url=https://books.google.com/books?id=_kYQAQAAMAAJ}}</ref> The metabolic process was identified in 1960s as catalysis by [[cytochrome P450]], which produces reactive species that can interact with the DNA to form [[adduct]]s, or product molecules resulting from the reaction of DNA and, in this case, cytochrome P450;<ref>{{Cite journal 
| last1 = Omura | first1 = T. 
| last2 = Sato | first2 = R. 
| title = A new cytochrome in liver microsomes 
| journal = The Journal of Biological Chemistry 
| volume = 237 
| pages = 1375–1376 
| year = 1962 
| issue = 4 
| doi = 10.1016/S0021-9258(18)60338-2 
| url = http://www.jbc.org/content/237/4/PC1375.long
| pmid = 14482007
| doi-access = free 
}}</ref><ref>{{Cite journal 
| last1 = Conney | first1 = A. H. 
| title = Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture 
| url = http://cancerres.aacrjournals.org/content/42/12/4875.long
| journal = Cancer Research 
| volume = 42 
| issue = 12 
| pages = 4875–4917 
| year = 1982 
| pmid = 6814745
}}</ref> the mechanism by which the PAH adducts give rise to mutation, however, is still under investigation.