Mechanisms of metabolism other than those mediated by the mixed function oxidases may be important in activating certain chemicals to their ultimate carcinogenic form. Prostagladin H synthetase is being used to activate compounds in the mouse lymphoma forward mutation assay. Modifications of the standard assay are necessary due to a high level of toxicity in this system. Initial experiments showed hydrogen peroxide to be a good substrate for this enzyme. However, mutagenicity results are confounded by the interaction of hydrogen peroxide with sodium pyrvate, a media component in this assay. Minimal treatment conditions and optional concentrations of purified enzyme have been determined. The possible mechanisms responsible for the formation of mutagenic metabolites induced by various peroxidase enzyme systems are being investigated. Selective inhibitors of the peroxidase are used to aid in the elucidation of these mechanisms. Studies include the identification of metabolites induced by this activation system.
