Comparative toxicity of arsenite metabolites in wild type cho cells and in cells deficient in excision repair cross-complementing 1 and 2

Arsenic (As) has been shown to alter one or more DNA repair processes. Excision repair cross-complementing 1 and 2 (ERCC1 and ERCC2) have shown to be associated with arsenic-induced toxicity and carcinogenicity. In this study, we investigated cytotoxic effects of various As metabolites in relation to two nucleotide excision repair genes: ERCC1 and ERCC2. Various arsenate (pentavalent) and arsenite (trivalent) metabolites were tested in ERCC1, ERCC2 deficient and wild type cells. Our results showed that in the selected concentration range pentavalent As metabolites; iAsV, MMAV and DMAV were not cytotoxic, unlike the trivalent As metabolites; iAsIII, MMAIII and DMAIII. The measured LC50 demonstrated a significant difference (p < 0.01) for iAsIII between the three cell lines, while MMAIII and DMAIII are more cytotoxic to all three cell lines. UV5 (ERCC2 deficient) cells also showed a lower resistance to iAsIII in comparison to AA8 (wild type) and UV20 (ERCC2 deficient) cells. This might be explained through the generation of hydrogen peroxide (H2O2), which is generated by increase of intracellular Ca2+ level. Generation of H2O2 in UV5 cells after incubation with iAsIII is significantly higher than AA8 and UV20 cells (p < 0.01). In conclusion, absence of ERCC2 leads to a increased generation of H2O2 by iAsIII in UV5 cells, which is in contrast to AA8 and UV20 cells.