Cytochrome P-450 isoenzyme content and monooxygenase activities in rat liver: effect of ontogenesis and pretreatment by phenobarbital and 3-methylcholanthrene.

The overall cytochrome P-450 content and the immunochemically determined concentrations of constitutive isoenzymes UT-A and UT-I and isoenzymes induced by phenobarbital (PB-B), pregnenolone 16 alpha-carbonitrile (PCN-E), beta-naphthoflavone (BNF-B) and isosafrole (ISF-G) were investigated in liver microsomes from developing rats and tentatively correlated with mono-oxygenase activities. In fetuses of untreated rat, although the cytochrome P-450 was easily quantified spectrally, none of the isoenzymes tested could be immunochemically detected. After birth, each isoenzyme develops in untreated animals with its own pattern of evolution. Mono-oxygenase activities exhibited different developmental pictures. Benzphetamine-N-demethylase and lauric acid 11-hydroxylase activities progressively increased up to adult values, aniline hydroxylase activity was maximal in 15-day-old animals and benzopyrene hydroxylase and lauric acid 12-hydroxylation were increased after birth until 15 days of age in both males and females and underwent a second increase in males. Pretreatment with phenobarbital resulted in the precocious onset of PB-B in fetal and neonatal rat liver accompanied by an increase in classically associated monooxygenase activities. The PCN-E concentration was enhanced by phenobarbital pretreatment only at 15 days and in older animals. BNF-B and benzo(a)pyrene hydroxylase activity were significantly increased by 3-methylcholanthrene whatever the age considered, whereas this inductive effect upon ISF-G concentration became effective only after 2 weeks of age. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, UT-A was faint in early neonates and intensified at 15 days.(ABSTRACT TRUNCATED AT 250 WORDS)