The mutagenicities of sodium bisulfite and glutathione, reported earlier, appear to be mediated through the formation of oxygen- containing free radicals. The mutagenicity of bisulfite to bacteria is related to its autoxidation rate in solution, and this value varies with pH, temperature, and presence of other substances in solution with sodium bisulfite. The autoxidation rate changes with pH and temperature (pH 7/37C more than pH 7/27C more than pH 5/37C more than pH 5/27C) and the mutagenic response increases as the rate decreases. The data suggest that for mutagenicity to occur, unoxidized bisulfite must be available to be taken up by the cells. The addition of ethanol, mannitol liver homogenate (S9), or oxoid broth enhanced the responses but did not change the directions of the trends. These data suggest a role for sulfur and radicals in the toxicity and mutagenicity of bisulfite. Glutathione is mutagenic to bacteria via its autoxidation which leads to the formation of hydrogen peroxide, which is a bacterial mutagen. The Salmonella strains that are most responsive to glutathione mutagenicity are also the most responsive to hydrogen peroxide. Other thiols (cysteine, penicillamine, cysteine ethyl ester, and cysteinylglycine) were mutagenic without exogenous metabolic activation and their mutagenicity was a function of the pH of the medium and the pKa of the thiol group. This supports the hypothesis that the spontaneous oxidation of these thiols, with the eventual formation of hydrogen peroxide, requires the initial formation of a thiolate anion.
