Foetal and neonatal development of cytochrome P-450 and cytochrome P-448 catalysed mixed function oxidases in the rat: induction by 3-methylcholanthrene.
Benzphetamine N-demethylase (cytochrome P-450) and ethoxyresorufin O-deethylase activities (cytochrome P-448) were determined in the growing neonate and foetus of control and 3-methylcholanthrene-pretreated rats. Ethoxyresorufin O-deethylase activity was highest in the 1-2-week-old animals and then decreased with age. The inducibility of this activity by 3-methylcholanthrene was low in the young animals, but increased with age. In contrast, benzphetamine N-demethylase activity in the control animals was low at birth and increased with age, and was not induced by 3-methylcholanthrene. In the foetal liver, ethoxyresorufin O-deethylase was the only activity present at higher levels than in the maternal liver. Transplacental administration of 3-methylcholanthrene failed to induce the foetal activities while the maternal liver showed the expected response. These observations demonstrate that cytochrome P-448 may be a predominant hepatic form in the foetus and neonate but cytochrome P-450 becomes a major form as the animal grows. The implications of these findings in chemical toxicity are discussed.
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D003580:Cytochromes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating