Induction of DNA double strand breaks by arsenite: comparative studies with DNA breaks induced by X-rays.

Chinese hamster ovary (CHO-K1) cell line and two of its DNA double strand break (DSB) repair deficient mutant cell lines, xrs-5 (Ku80 mutant) and irs-20 (DNA-PKcs mutant), were treated with various concentrations of sodium arsenite for 2.5 hrs, and the colony forming abilities were studied. The wild type cells showed the highest cell survival, while xrs-5 cells showed the lowest survival, and irs-20 cells had an intermediate survival. These results are very similar to the cell survival curves induced by x-rays in these three cell lines. Our data also shows the dose dependent induction of DNA DSBs in these cell lines exposed to arsenite. However, in order to obtain a similar cell survival in wild type cells, twice as many DNA DSBs are necessary with arsenite exposure when compared with x-rays, suggesting that the types of DNA lesions leading to DSB induced by arsenite are different from those by x-rays. Based on these data, further mechanistic investigations including the involvement of DNA DSB repair proteins are warranted in the recovery process from arsenic exposure