Hepatic cytochrome P450 enzyme imprinting in adult rat by neonatal benzo[a]pyrene administration.

The effect of neonatal exposure to benzo[a]pyrene (BaP) on the hepatic cytochrome P450 of male and female adult rats has been examined. Newborn rats (< 24 h old) were injected with a single dose of BaP (1 mg/rat, s.c.) and killed after 110 days. In both sexes, body and liver weight, microsomal protein content, and total cytochrome P450 were unchanged. Cytochrome P450 1A2 protein content and 7-ethoxyresorufin O-deethylase activity were significantly decreased (p < 0.05) in males, whereas these were unaltered in females. Male-specific cytochrome P450 2C11 of male rats was significantly increased as shown by Western blot and increased testosterone 2 alpha- and 16 alpha-hydroxylase activities by 29% (p < 0.01) and 22% (p < 0.05), respectively. Female-specific cytochrome P450 2C12 protein content was unaltered in females. In addition, the level of free hepatic glucocorticoid receptor in adult males was elevated by 35% after BaP exposure, whereas it was unchanged in adult females. These results indicate, for the first time, that neonatal BaP exposure results in gender-specific lasting effects on hepatic cytochrome P450 1A2, cytochrome P450 2C11, and glucocorticoid receptors in adult male rats, whereas these parameters are unchanged in adult female rats.