Effects of exogenous cysteine on inorganic and organic arsenicals-induced cytolethality

Inorganic arsenicals are distinctly toxic and carcinogenic to humans. Inorganic arsenite (As-III) and arsenate (As-V) are enzymatically methylated to monomethylarsonic acid (MMAsV) and dimethylarsinic acid (DMAsV) in mammals. Recent reports indicate that cytotoxic trivalent methylated arsenicals are produced through methylation of inorganic arsenicals and are involved in arsenic poisoning. Some previous studies have suggested that a typical thiol reagent cysteine (Cys) can reduce pentavalent arsenicals to trivalent arsenicals and might be able to enhance arsenic cytolethality. However, not much is known concerning the effects of exogenous Cys on the cytolethality of arsenicals. In this study, we examined the effects of exogenous Cys on the cytolethality induced by inorganic and organic arsenicals using rat liver cells. Cys prevented inorganic As-III-induced cytolethality. In contrast, when more than 5 mm Cys was incubated with millimolar levels of MMAsV or DMAsV, MMAsV- and DMAsV-induced cytolethality significantly increased; this cytolethality might have been caused by the generation of trivalent methylated arsenicals. However, Cys at a concentration of less than 5 mm decreased the MMAsV- and DMAsV-induced cytolethality. These findings suggest that high concentrations of both arsenicals and Cys are required to form trivalent methylated arsenicals and to induce significant cytolethality. Copyright (c) 2006 John Wiley & Sons, Ltd.