Effect of microsomal preparations and induction on cytochrome P-450-dependent monooxygenases in fetal and neonatal rat liver

Abstract

A study of the sedimentation behavior of fetal and neonatal rat liver microsomes allowed a better recovery of a less contaminated microsomal fraction, especially by the use of an EDTA-containing buffer. The specific cytochrome P-450 content and related catalytic activities in the 105,000 g pellet of fetal and neonatal liver were thus much higher than usually reported, while molecular activities were comparable to adult ones.The transplacental inducing effects of phenobarbital and 3-methylcholanthrene on the monooxygenase system were studied in microsomes prepared by the modified procedure and compared to results obtained in crude liver homogenate: 3-methylcholanthrene induces a net biosynthesis of cytochrome P-450 in fetal liver, whereas phenobarbital produces only a premature transformation of rough into smooth endoplasmic reticulum, which decreases the ‘contamination’ of the 105,000 g pellet by ribosomal protein. As a result, the specific cytochrome P-450 content of the microsomal fraction appears to be increased by phenobarbital, though there is no true induction of the monooxygenase system in near-term rat fetus.