Developmental regulation of cytochrome P-450 genes in the rat

Abstract

Synthetic oligomer probes were used in hybridization experiments to investigate the developmental regulation of cytochrome P-450 (P-450) genes in rat liver. Transplacental induction by phenobarbital of P-450b and P-450e mRNAs was not detectable in fetal rat livers prior to day 21 of gestation. The levels of these mRNAs increased approximately 2-fold from gestational day 21 to day 22 in phenobarbital-induced liver. P-450b and P-450e mRNAs were shown to be adenylated and the fractions associated with polysomes were similar in both fetal and adult livers. No P-450b or P-450e mRNAs were detected in fetal lung and kidney RNA preparations regardless of pretreatment. Southern blot data utilizing fetal liver DNA suggests that responsiveness to xenobiotic induction during development is not attained by rearrangement of P-450b or P-450e genes. Experiments with probes specific for P-450c and P-450d failed to detect their respective mRNAs in fetal livers from 3-methylcholanthrene (3-MC)-treated or untreated rats. Both species were detectable in 3-MC-treated rats 1 week after birth. The levels of 3-MC-inducible P-450c and P-450d mRNAs increased with age and peaked approximately 3 weeks after birth. Hepatic P-450d mRNA levels in 3-MC-treated or control rats was consistently higher than P-450c mRNA levels at all ages studied.