Crosslink formation between DNA and nuclear proteins by in vivo and in vitro exposure of cells to dimethylarsinic acid.

DNA damage induced by arsenics, particularly by dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, was investigated. DNA-protein crosslinks, similarly to DNA single-strand breaks, were induced in mouse and human culture cells by the treatment with DMAA. The crosslinks were sensitive to treatment with guanidine and hydroxylamine, suggesting that the DNA linkage sites in proteins were serine and threonine residues of H1 histone and of nonhistone proteins and that the linkage occurred through a phospho-nitrogen bond. The type of crosslinks was different from that induced by X-ray radiation. Of the radicals produced in the further metabolic processing of DMAA, the dimethylarsenic peroxyl radical rather than the superoxide anion radical is likely responsible for the formation of crosslinks, similar to the case of DNA single-strand breaks.