Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species.
Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.
Hei
T K
TK
Center for Radiological Research, College of Physicians and Surgeons, School of Public Health, Columbia University, New York, NY 10032, USA. TKH1@Columbia.edu
Liu
S X
SX
Waldren
C
C
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D016466:CHO Cells; D002880:Chromosomes, Human, Pair 11; D006224:Cricetinae; D006801:Humans; D006822:Hybrid Cells; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D001151:Arsenic