Enzymatic Conversion of Benzo[a]pyrene

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Abstract
Hydroxylating and DNA-binding activity is increased in lung and liver microsomes after induction of enzyme activity by injecting benzo[a]pyrene (BaP) into intact rats. Overall enzymatic activity increases more in liver than in lung, and DNA-binding increases more than hydroxy product formation in microsomes from liver as compared to lung. Three major metabolites, detected by chromatography of a hexane-acetone extract after incubation of BaP labeled with tritium with preinduced liver microsomes, are reduced sharply by hematin at 5 x 10-5M, and eliminated by 2.5 x 10-4M. The greatest reduction was of a peak identical with a standard sample of 3-hydroxy-BaP. Hematin reduced DNAbinding to a greater degree than metabolite production. This suggests that hematin interferes with metabolic conversion of BaP to a DNA-binding product. The latter product may be a precursor of 3-OH-BaP since both DNA-binding and 3-OH-BaP production are similarly suppressed.