Recently, inorganic
arsenite (iAs(III)) and its mono- and dimethylated metabolites have been examined for their interference with the formation and repair of
benzo[a]pyrene diol
epoxide (
BPDE)-induced
DNA adducts in human cells (Schwerdtle, ., Walter, I., and Hartwig, A. (2003) DNA Repair 2, 1449 - 1463). iAs(III) and
monomethylarsonous acid (
MMA(III)) were found to be able to enhance the formation of
BPDE-DNA adducts, whereas
dimethylarsinous acid (DMA(III)) had no enhancing effect at all. The anomaly manifested by DMA(III) prompted us to further investigate the effects of the three trivalent
arsenic species on the formation of
BPDE-DNA adducts. Use of a nucleotide excision repair (NER)-deficient
Xeroderma pigmentosum complementation group A cell line (GM04312C) allowed us to dissect DNA damage induction from DNA repair and to examine the effects of
arsenic on the formation of
BPDE-DNA adducts only. At concentrations comparable to those used in the study by Schwerdtle et al., we found that each of the three trivalent
arsenic species was able to enhance the formation of
BPDE-DNA adducts with the potency in a descending order of
MMA(III) > DMA(III) > iAs(III), which correlates well with their cytotoxicities. Similar to iAs(III), DMA(III) modulation of
reduced glutathione (GSH) or total
glutathione S-transferase (GST) activity could not account for its enhancing effect on
DNA adduct formation. Additionally, the enhancing effects elicited by the trivalent
arsenic species were demonstrated to be highly time-dependent. Thus, although our study made use of short-term assays with relatively high doses, our data may have meaningful implications for
carcinogenesis induced by chronic exposure to
arsenic at low doses encountered environmentally.