title: Arsenic Disruption of DNA Damage Responses-Potential Role in Carcinogenesis and Chemotherapy.
abstract: Arsenic is a Class I human carcinogen and is widespread in the environment. Chronic arsenic exposure causes cancer in skin, lung and bladder, as well as in other organs. Paradoxically, arsenic also is a potent chemotherapeutic against acute promyelocytic leukemia and can potentiate the cytotoxic effects of DNA damaging chemotherapeutics, such as cisplatin, in vitro. Arsenic has long been implicated in DNA repair inhibition, cell cycle disruption, and ubiquitination dysregulation, all negatively impacting the DNA damage response and potentially contributing to both the carcinogenic and chemotherapeutic potential of arsenic. Recent studies have provided mechanistic insights into how arsenic interferes with these processes including disruption of zinc fingers and suppression of gene expression. This review discusses these effects of arsenic with a view toward understanding the impact on the DNA damage response.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA. clarisse.muenyi@louisville.edu.
authors.forename: Clarisse S
authors.initials: CS
authors.lastname: Muenyi
authors.affiliation: Departments of Radiation Oncology and Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109-2800, USA. ljungman@med.umich.edu.
authors.forename: Mats
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA. jcstates@lousiville.edu.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: States
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D001151:Arsenic
keywords: DNA damage response; DNA repair; MSH2; XPC; arsenic; ubiquitination