Different tissue responses of mixed function oxidases and detoxifying enzymes to aflatoxin B1 administration in the...

The carcinogenic effects of aflatoxin B1 have been related to the formation of an active intermediate metabolite, an epoxide produced via the cytochrome P-450-mediated mixed function oxidase. The toxicity of this intermediate is dependent on metabolic transformations by enzymes such as aryl hydrocarbon hydroxylase, glutathione S-transferase and glutathione peroxidase. Like the mixed function oxygenase, these enzymes are inducible, and dependent on the action of specific drugs and inducers. The present study describes the effect of a single sublethal i.p. dose (6 mg/kg body wt) of aflatoxin B1 on the specific activities of microsomal demethylases, aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase and glutathione peroxidase in rat liver, kidney, lung, brain and adrenals. The enzymes were assayed 24 h after the toxin treatment. Among the different tissues, only liver AHH showed an induction on toxin treatment whereas those of kidney and brain declined. Microsomal demethylase was also high in liver and low in kidney. However, no significant alteration was induced by aflatoxin B1 on glutathione S-transferase and glutathione peroxidase activities in the various tissues examined except the adrenals, which showed a significant increase. The present study revealed that the reaction sequence for metabolic transformation of aflatoxin B1 is more complex than foreseen from the activities of these inducible metabolite-transforming enzymes.