MUTAGENICITY OF COBALT AND REACTIVE OXYGEN PRODUCERS

Oxidative stress has been implicated in carcinogenesis yet there are c hemicals that produce oxidative stress that are not carcinogenic. Muta tions are the inherited results of DNA damage and are critical events in carcinogenesis. The mutagenicity of oxidative stress induced by per oxide, paraquat and cobalt compounds was examined in transgenic gpt(+) Chinese hamster cell lines (G12 and G10). These two cell lines are kn own to be more sensitive to mutagens such as X-rays and UV than their parental V-79 cells. In these studies, the mutagenic activity of cobal t chloride, a metal that induces oxidative stress but is not carcinoge nic, was measured to be 7.7 times higher than the spontaneous mutant f requency in G12, but was only 1.5 to 2.5 times higher than spontaneous mutant frequency in G10 cells. The mutant frequency of cobalt sulfide was somewhat lower. Hydrogen peroxide was found to be only weakly mut agenic in G12 cells, and treatment of cells with a combination of hydr ogen peroxide and cobalt did not alter the mutation frequency induced by cobalt sulfide alone. Paraquat did not elicit mutagenesis in either cell line. These results indicate that agents producing oxidative str ess are not necessarily mutagenic and these results are discussed in t he context of the oxidative stress produced by other carcinogens such as nickel compounds.