Protein oxidation and amino acid-DNA crosslinking by nickel compounds in intact cultured cells.

Oxidative damage induced by NiCl2 to protein has been investigated. We found that nickel induced a dose-dependent increase in the oxidation of bovine serum albumin (BSA) as detected by carbonyl formation in the presence of H2O2 in vitro, as well as producing carbonyl of proteins in intact cultured Chinese hamster ovary (CHO) cells. Other metals capable of producing oxidative damage to BSA in the presence of H2O2 included Cu, Co, Fe, and chromate. However, Cd2+, Hg2+, and Pb2+ were not active even in the presence of H2O2. As an indicator of nickel-induced genotoxic damage, the crosslinking of amino acids to DNA was also examined. Cysteine, histidine, and tyrosine were increased in their association with DNA based upon their persistent binding to DNA following washes with EDTA or SDS. The results suggest that DNA-protein or DNA-amino acids crosslinks induced by nickel may result from interaction of the nickel-oxidized carbonyl group of protein, peptides, and free amino acids.