Effects of various inducers on the activities of cytochrome P-450-mixed function oxidases and aflatoxin B1 activation in microsomes of hamster livers.
The effects of various inducers on the activities of drug-metabolizing enzymes including aflatoxin B1 activation were studied in Syrian golden hamsters. Activity for aflatoxin B1 was determined by aflatoxin B1-DNA adducts formation. The treatments of hamsters with 3-methylcholanthrene, alpha-naphthoflavone and benzo(a)pyrene elevated markedly the activity for aflatoxin B1 by 2460, 1380 and 450%, respectively. Phenobarbital induced slightly and isosafrole and ethanol did not induce the activity for aflatoxin B1. Pregnenolone-16 alpha-carbonitrile decreased aflatoxin B1 activation to 51% of that of the non-treated animals. These results were in good accordance with the induction rate of a form of cytochrome P-450 (P-450AFB) which has potent activity to aflatoxin B1. Characteristics in the induction of mixed function oxidases of hamsters by these inducers, especially in respect to benzo(a) pyrene metabolizing enzyme, seemed to differ from those of rats. These results suggest that the activity for aflatoxin B1 in hamster is inducible by 3-methylcholanthrene-type inducers and that hamster is a suitable animals model to study the mechanism of aflatoxin B1-hepatocarcinogenesis.
Sunouchi
M
M
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Fukuhara
M
M
Ohno
Y
Y
Takanaka
A
A
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000493:pharmacokinetics*; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000032:analysis / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase; D010088:Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism*
D000348:Aflatoxins; D001571:Benzoflavones; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D004247:DNA; D016604:Aflatoxin B1; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase