DNA binding of aflatoxin B1 by co-oxygenation in mouse embryo fibroblasts C3H/10T1/2.
The mechanism of activation of aflatoxin B1 to ultimate metabolites capable of DNA binding was investigated in mouse embryo fibroblasts C3H/10T1/2. 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 AFB1-binding to maximally 60%. The antioxidant glutathione 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 AFB1-metabolism in 10T1/2 cells. The observation that the phospholipase A2 inhibitor p-bromophenacylbromide diminished AFB1-DNA binding supports the notion that AFB1, because it is membrane-active, may enhance its own co-oxidative metabolism by stimulating the arachidonic acid cascade.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002999:Clone Cells; D004247:DNA / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010084:Oxidation-Reduction
D000348:Aflatoxins; D004247:DNA; D016604:Aflatoxin B1