Mutagenicity of nitroxide-free radicals

Stable nitroxides were found to be mutagenic using Salmonella typhimurium tester strain TA 104, a strain chosen on the basis of its high sensitivity to oxidative damage. Nitroxide mutagenicity was dramatically increased in the presence of the superoxide radical generating system, xanthine oxidase/hypoxanthine, and it was suppressed in cells carrying the oxyR1 mutation, which causes induction of enzymes protecting against oxidative stress. As nitroxide-free radicals occur biologically, e.g., in the metabolism of aromatic amines, these radical-induced mutations could be a model for the carcinogenicity observed with these compounds.