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Although its mode of action has yet to be fully elucidated, oxidative DNA damage has been suggested. A series of DNA repair\u2010defective human and hamster cell lines associated with sensitivity to oxidative agents were examined for their response to arsenic\u2010induced cytotoxicity. Only the Ataxia telangiectasia (AT) cells displayed a marked hypersensitive response (greater than twofold). The protective role of the ATM protein was confirmed by the normal response to arsenic displayed by AT cells expressing wild\u2010type ATM. Although the ATM protein plays a pivotal role in response to DNA double\u2010strand breakage, none of the other cell lines with defects in double\u2010strand break repair displayed a similar hypersensitivity. Further examination indicated that concentrations of sodium arsenite as high as 1 mg\/l do not generate significant levels of double\u2010strand breaks. Our data suggest that the ATM protein functions in an important but different capacity in the cellular response to arsenic toxicity than it does in response to agents that generate double\u2010strand breaks, such as ionizing radiation. Furthermore, the lack of hypersensitivity to arsenic displayed by the other cell lines calls into question the hypothesis that DNA damage is a significant factor in arsenic cytotoxicity.<\/jats:p>","DOI":"10.1096\/fj.02-0093fje","type":"journal-article","created":{"date-parts":[[2003,10,20]],"date-time":"2003-10-20T20:21:40Z","timestamp":1066681300000},"page":"2310-2312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic predisposition to the cytotoxicity of arsenic: the role of DNA damage and ATM"],"prefix":"10.1096","volume":"17","author":[{"given":"Nan","family":"Mei","sequence":"first","affiliation":[{"name":"Department of Experimental Oncology Cross Cancer Institute 11560 University Avenue Edmonton Alberta T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology Cross Cancer Institute 11560 University Avenue Edmonton Alberta T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology Cross Cancer Institute 11560 University Avenue Edmonton Alberta T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Z.","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 2G3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hanson","sequence":"additional","affiliation":[{"name":"Division of Epidemiolgy Cross Cancer Institute 11560 University Avenue Edmonton Alberta T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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