Dose-dependent induction of the microsomal monooxygenase system by phenobarbital and 3-methylcholanthrene in the ad libitum and calorie-restricted female rat.
1. We characterized the dose-dependent induction of the microsomal monooxygenase system by phenobarbital (PB) and 3-methylcholanthrene (MC) in the female Fischer 344 rat, which was either calorie restricted (CR) or fed ad libitum (AL). 2. Maximal induction of the major inducible isozymes (2B1/2B2 or 1A1) in rat was achieved at the lowest of the inducer doses employed (10 mg/kg body weight) in both feeding groups. 3. The patterns of dose-dependent PB induction and its magnitude differed between total P450 induction and induction of catalytic activities in AL and CR groups, whereas no differences between CR and AL rat were found in either spectrally detected P450 or EROD activity patterns of dose-dependent MC induction. 4. Calorie restriction increased the inducibility of some hepatic drug-metabolizing enzyme activities. 5. Monoclonal antibody-directed inhibition of MC-induced ethoxyresorufin O-deethylation (EROD) was 55-60% at all induction levels in AL rat and 65-70% in CR rat, while MAb inhibition of PB-induced pentoxyresorufin O-depenthylation (PROD) averaged about 55% in AL and 60% in CR rat.
Alterman
M A
MA
Department of Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station 77843, USA.
Carvan
M J
MJ
Busbee
D L
DL
D000818:Animals; D000911:Antibodies, Monoclonal; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry; D004032:Diet; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D004790:Enzyme Induction; D005260:Female; D016130:Immunophenotyping; D008099:Liver / Q000254:growth & development; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D000911:Antibodies, Monoclonal; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010634:Phenobarbital