Differential effects of dietary BHA on hepatic enzyme activities and benzo[a]pyrene metabolism in male and female NMRI mice

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Abstract
The effect of dietary 2(3)- tert -butyl-4-hydroxy-anisole (BHA) alone and in combination with intraperitoneal injections of 3-methylcholanthrene (MC), on hepatic enzyme activities and benzo[a]pyrene (BP) metabolism was compared in male and female NMRI mice. In general, the characteristic induction pattern following dietary BHA administration in female mice could also be seen when male mice were used. The increase in epoxide hydrolase and cytosolic glutathione S-transferase following BHA feeding was however not as pronounced in males as in females. Also, MC treatment appeared to counteract the induction of GST activity by BHA in females but had no such effect in males. Liver microsomes from untreated male mice catalyzed the metabolism of BP less efficiently than did microsomes from females. BHA treatment increased this activity in both sexes to a comparable extent and the overall activity was the same in males and females having received MC. The pattern of BP metabolites was altered following BHA treatment. In general, an increase in BP-4,5-diol and a decrease in 9-OH-BP was observed. This pattern was also noticed when microsomes from MC treated and MC + BHA treated animals were compared. MC treatment alone increased the amount of BP-7,8-diol, the quinones and the phenols. The present report indicates that several factors may contribute to the response to dietary BHA in mice. Whether this has any consequence in regard to this compound's anticarcinogenic effect remains to be elucidated.