Role of oxidative damage in the genotoxicity of arsenic

Arsenic is a well-established human carcinogen and is ubiquitous in the environment. For decades, arsenic has been considered to be a nongenotoxic carcinogen because it is only weakly active or, more often, completely inactive in bacterial and mammalian cell mutation assays. In this review, evidence is presented that when assayed using model systems in which both intragenic and multilocus mutations can readily be detected, arsenic is, indeed, found to be a strong, dose-dependent mutagen which induces mostly multilocus deletions. Furthermore, the roles of reactive oxygen and reactive nitrogen species in mediating the genotoxic response are presented in a systematic and logical fashion in support of a working model. The data suggest that antioxidants may be a useful interventional treatment in reducing the deleterious effects of arsenic. (C) 2004 Elsevier Inc. All rights reserved.