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Ames test
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==Ames test and carcinogens== Mutagens identified via Ames test are also possible carcinogens, and early studies by Ames showed that 90% of known carcinogens may be identified via this test.<ref name="ames75">{{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 = 5135β9 | date = December 1975 | pmid = 1061098 | pmc = 388891 | doi = 10.1073/pnas.72.12.5135 | bibcode = 1975PNAS...72.5135M | doi-access = free }}</ref> Later studies however showed identification of 50β70% of known carcinogens.{{Citation needed|date=March 2012}} The test was used to identify a number of compounds previously used in commercial products as potential carcinogens.<ref>{{cite journal | vauthors = Ames BN | title = Identifying environmental chemicals causing mutations and cancer | journal = Science | volume = 204 | issue = 4393 | pages = 587β93 | date = May 1979 | pmid = 373122 | doi = 10.1126/science.373122 | url = http://legacy.library.ucsf.edu/documentStore/e/p/c/epc74e00/Sepc74e00.pdf | author-link1 = Bruce Ames | jstor = 1748159 | bibcode = 1979Sci...204..587A }}</ref> Examples include [[tris(2,3-dibromopropyl)phosphate]], which was used as a flame retardant in plastic and textiles such as children's sleepwear,<ref>{{cite journal | vauthors = Prival MJ, McCoy EC, Gutter B, Rosendranz HS | title = Tris(2,3-dibromopropyl) phosphate: mutagenicity of a widely used flame retardant | journal = Science | volume = 195 | issue = 4273 | pages = 76β8 | date = January 1977 | pmid = 318761 | doi = 10.1126/science.318761 | bibcode = 1977Sci...195...76P }}</ref> and [[furylfuramide]] which was used as an antibacterial additive in food in Japan in the 1960s and 1970s. Furylfuramide in fact had previously passed animal tests, but more vigorous tests after its identification in the Ames test showed it to be carcinogenic.<ref> {{Citation | last = Hayatsu | first = Hiroka | title = Mutagens in Food: Detection and Prevention | publisher = [[CRC Press]] | year = 1991 | pages = 286 pages | url = https://books.google.com/books?id=eQyMCWRIVf4C&q=carcinogen+preservative+(furylfuramide%7Caf2)&pg=RA1-PA1 |isbn = 978-0-8493-5877-7 }}</ref> Their positive tests resulted in those chemicals being withdrawn from use in consumer products. One interesting result from the Ames test is that the dose response curve using varying concentrations of the chemical is almost always linear,<ref name="ames75"/> indicating that there is no threshold concentration for mutagenesis. It therefore suggests that, as with radiation, there may be [[Linear no-threshold model|no safe threshold]] for chemical mutagens or carcinogens.<ref>{{cite book | first = Andrew | last = Teasdale | name-list-style = vanc | title = Genotoxic Impurities: Strategies for Identification and Control |publisher=Wiley-Blackwell |year=2011 |isbn=978-0-470-49919-1 }}</ref><ref name="linear">{{cite journal | vauthors = Tubiana M | title = The carcinogenic effect of exposure to low doses of carcinogens | journal = British Journal of Industrial Medicine | volume = 49 | issue = 9 | pages = 601β5 | date = September 1992 | pmid = 1390264 | pmc = 1039303 | doi = 10.1136/oem.49.9.601 }}</ref> However, some have proposed that organisms could tolerate low levels of mutagens due to protective mechanisms such as [[DNA repair]], and thus a threshold may exist for certain chemical mutagens.<ref>{{cite journal | vauthors = Jenkins GJ, Doak SH, Johnson GE, Quick E, Waters EM, Parry JM | title = Do dose response thresholds exist for genotoxic alkylating agents? | journal = Mutagenesis | volume = 20 | issue = 6 | pages = 389β98 | date = November 2005 | pmid = 16135536 | doi = 10.1093/mutage/gei054 | doi-access = free }}</ref> Bruce Ames himself argued against linear dose-response extrapolation from the high dose used in carcinogenesis tests in animal systems to the lower dose of chemicals normally encountered in human exposure, as the results may be false positives due to [[mitogenic]] response caused by the artificially high dose of chemicals used in such tests.<ref>{{cite journal | vauthors = Forman D | title = Ames, the Ames test, and the causes of cancer | journal = BMJ | volume = 303 | issue = 6800 | pages = 428β9 | date = August 1991 | pmid = 1912830 | pmc = 1670593 | doi = 10.1136/bmj.303.6800.428 }}</ref><ref>{{cite journal | vauthors = Ames BN, Gold LS | title = Chemical carcinogenesis: too many rodent carcinogens | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 19 | pages = 7772β6 | date = October 1990 | pmid = 2217209 | pmc = 54830 | doi = 10.1073/pnas.87.19.7772 | bibcode = 1990PNAS...87.7772A | doi-access = free }}</ref> He also cautioned against the "hysteria over tiny traces of chemicals that may or may not cause cancer", that "completely drives out the major risks you should be aware of".<ref>{{cite journal | vauthors = Twombly R | title = Federal carcinogen report debuts new list of nominees | journal = Journal of the National Cancer Institute | volume = 93 | issue = 18 | pages = 1372 | date = September 2001 | pmid = 11562386 | doi = 10.1093/jnci/93.18.1372 | doi-access = free }}</ref> The Ames test is often used as one of the initial screens for potential drugs to weed out possible carcinogens, and it is one of the eight tests required under the [[Federal Insecticide, Fungicide, and Rodenticide Act|Pesticide Act]] (USA) and one of the six tests required under the [[Toxic Substances Control Act of 1976|Toxic Substances Control Act]] (USA).<ref>{{cite book |title=The Molecular Basis of Cancer | first1 = Peter B | last1 = Farmer | first2 = John M | last2 = Walker | name-list-style = vanc |url=https://books.google.com/books?id=t9ENAAAAQAAJ |publisher=Krieger Publishing Company |year=2006 |isbn=978-0-7099-1044-2 }}</ref>
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