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.
Fujita
I
I
Department of Pathology, College of Medicine, University of California at Irvine 92717, USA.
Sindhu
R K
RK
Kikkawa
Y
Y
D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes; D015786:Cytochromes b5 / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism
D003580:Cytochromes; D007527:Isoenzymes; D011965:Receptors, Glucocorticoid; D001564:Benzo(a)pyrene; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D039181:Steroid 16-alpha-Hydroxylase; D010089:Oxidoreductases, N-Demethylating