Effect of enzyme induction on the metabolism of benzo(a)pyrene and 3'-methyl-4-monomethylaminoazobenzene in the pregnant and fetal rat.

Treatment of pregnant rats with as little as 0.5 mg of BP per kg p.o. for 3 days stimulated the metabolism of the hydrocarbon by maternal liver and placenta, while a 20-fold higher dose of this hydrocarbon was necessary for stimulation of BP hydroxylation in fetal liver. BP metabolism was increased in fetal and maternal liver microsomes after treatment of pregnant rats with 3-methylcholanthrene, and this increase in enzyme activity was paralleled by an increase in microsomal hemoprotein concentration, as measured by the change in absorbance at 450 or 455 nm when CO or ethyl isocyanide, respectively, was added as the ligand to reduced liver microsomes. Administration of 3-methylcholanthrene also increased the ratio of the peak at 455 nm to the peak at 430 nm in the ethyl isocyanide difference spectra and shifted by 2 nm the maximum absorption of the 450 nm peak to a shorter wavelength in the CO-induced difference spectra of maternal and fetal liver microsomes, thus indicating a qualitative alteration of the microsomal hemoprotein(s). Treatment of pregnant rats with phénobarbitalincreased the hydroxylation of BP and increased the hemoprotein concentration in maternal liver microsomes, but no effect was observed on these same parameters in fetal liver microsomes. The in vivo metabolism of BP-3H was increased in pregnant