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METHYLATION INACTIVATES PENTAVALENT ARSENIC SPECIES BUT ACTIVATES TRIVALENT ARSENIC SPECIES TO POTENT GENOTOXICANTS
Citation:
Brock, K H., E. Winkfield, AND M J. Mass. METHYLATION INACTIVATES PENTAVALENT ARSENIC SPECIES BUT ACTIVATES TRIVALENT ARSENIC SPECIES TO POTENT GENOTOXICANTS. Presented at annual meeting of Environmental Mutagen Society, Anchorage, Alaska, 4/27/02-5/2/02.
Description:
Methylation Inactivates Pentavalent Arsenic Species but Activates Trivalent Arsenic Species to Potent Genotoxicants
The sensitivity ofhumans to arsenic-induced cancer is thought to be related in part to the limited ability of humans to detoxify arsenic. Recently, methyl- and dimethyl-Aslll have been detected in urine from individuals exposed to arsenic in drinking water. In our study, synthetic monomethyl- and dimethyl-Aslll, as methyloxoarsine (MAs Ill) and iododimethylarsine (DMAsIll), were assayed in vitro in the mouse lymphoma L5178Y Tk+'- assay (MLA). We report that methylated-AsIll species induce mutations at the Tk+'-locus at concentrations 28- to 50-fold lower than inorganic arsenite (iAsm) and arsenate (iAs). Some researchers have hypothesized that methylation detoxifies arsenic-a hypothesis that would predict that the methylated arsenicals would be less genotoxic than the inorganic arsenicals. In support of this hypothesis, we reported in previous work that the methylated Asv species, methylarsonic acid (MAs) and dimethylarsinic acid (DMAs), were significantly less potent mutagens that iAs. However, as we report here, this hypothesis is not true for the trivalent forms of arsenic. Our results in the MLA show that the mutagenic potencies of the arsenic compounds (expressed as mutant ency/~M) rank as follows: MAsm (452) > DMAsm (38) > iAslll (16) > iAsv (9) >> MAsv (0.009) > DMAsv (0.002). Thus, there is a 250,OOO-fold difference in mutagenic potency between MASIll and DMAsv. These results show that methylation of pentavalent arsenic is a detoxification process but methylation of trivalent arsenic is an activation process.
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