DNA binding of aflatoxin B 1 by co-oxygenation in mouse embryo fibroblasts [formula omitted

Abstract

The mechanism of activation of aflatoxin B 1 to ultimate metabolites capable of DNA binding was investigated in mouse embryo fibroblasts C3H 10T 1 2 . The contribution of co-oxygenation reactions which are coupled to arachidonic acid metabolism was assessed by the use of inhibitors of prostaglandin endoperoxide synthetase and lipoxygenase. Indomethacin and 5,8,11,14-icosatetraynoic acid inhibited AFB 1-binding to maximally 60%. The antioxidant glutathoone was also inhibitory while CuZn superoxide dismutase had no effect or slightly stimulated binding at high concentrations. These results indicate that co-oxygenation plays a major role in AFB 1-metabolism in 10T 1 2 cells. The observation that the phospholipase A 2 inhibitor p-bromophenacylbromide diminished AFB 1-DNA binding supports the notion that AFB 1, because it is membrane-active, may enhance its own co-oxidative metabolism by stimulating the arachidonic acid cascade.