Regioselective inhibition of benzo[a]pyrene metabolism by butylated hydroxyanisole

The effects of butylated hydroxyanisole (BHA) on the metabolism of benzo[a]pyrene (BP) were investigated with mouse hepatic microsomes. Microsomes from BHA-fed mice showed a higher activity in catalyzing the formation of most metabolites from BP but a much lower activity in the formation of 9-hydroxyBP than control microsomes. Dietary BHA treatment enhanced the total metabolism of BP but decreased the microsomal metabolism of BP-7,8-diol, especially the formation of BP-trans-7,8-diol-anti-9,10-oxide. The altered metabolism of BP is believed to be due to the induction of new cytochrome P-450 species by dietary BHA. Consistent with this interpretation is the observation that the treatment also decreased the K_m and increased the V_max of ethoxycou-marin O-dealkylase. Short-term treatment (BHA administered p.o.) and in vitro added BHA were shown to inhibit BP metabolism. Thus, BHA can affect BP metabolism by exerting its inhibitory effect directly and by altering the composition of microsomal monooxygenase enzymes after a few days of exposure.