Comparison of hepatic drug-metabolizing enzymes induced by 3-methylcholanthrene and phenobarbital between pre- and postnatal rats.

Effects of 3-methylcholanthrene (3MC) and phenobarbital (PB) on the hepatic drug-metabolizing enzyme system in fetal liver of rats were investigated. Intraperitoneal administration of 3MC (25 mg/kg, 72 and 48 hr before death) to pregnant rats significantly increased hexobarbital (HB) and aminopyrine (AM)-metabolizing activities in fetuses on the 21st day of gestation to 148.0 and 150.6% of control fetuses, respectively. In contrast, HB and AM-metabolizing activities in 4-day-old neonates and mothers were decreased by administration of 3MC on the 21st day of gestation. Benzo[a]pyrene (BP)-metabolizing activity, NADPH-cytochrome c reductase activity, and cytochrome P-450 content in 3MC-treated fetuses were significantly increased to 2143.6, 137.6, and 323.8% of the control, respectively. Following 3MC administration, the maximum absorption of the cytochrome P-450-CO difference spectra in liver microsomes of fetuses was observed at 449-450 nm. The induction profile following 3MC administration in the fetal livers was different from that in the neonatal and the maternal livers. On the other hand, intraperitoneal administration of PB (60 mg/kg, 72, 48, and 24 hr before death) significantly increased HB, AM, and BP-metabolizing activities in fetal livers to 263.7, 231.0, and 151.2% of the respective controls. The profile induced by PB in the fetal livers was similar to that in maternal livers. These results suggest that HB and AM-metabolizing enzymes in fetal livers treated with 3MC or PB possess the capacity to be induced, and the responsiveness of the drug-metabolizing enzyme system to 3MC during the prenatal stage may differ from the postnatal stage.