Aflatoxin B1-specific cytochrome P-450 isozyme (P-450-AFB) inducible by 3-methylcholanthrene in golden hamsters.
Hepatic microsomes of polychlorinated biphenyl (PCB)-treated Syrian Golden hamsters possessed a higher potency toward aflatoxin B1 activation, based on the Ames test, than other animal species. This activity was induced in hamsters preferentially by treatment with 3-methylcholanthrene rather than phenobarbital. The contribution of an isozyme of cytochrome P-450 (P-450-AFB) to the activity of hamster livers for aflatoxin B1 was studied. P-450-AFB, purified from 3-methylcholanthrene-treated hamster livers, was shown to possess the highest activation of aflatoxin B1 in the Ames test. The quantification of this isozyme by a fluorometric sandwich enzyme-linked immunosorbent assay (ELISA) demonstrated that P-450-AFB was induced mainly in Syrian Golden hamsters but not in Chinese hamsters, or in other species. This isozyme constitutes approximately 40% of the total cytochrome P-450 of the hepatic microsomes from 3-methylcholanthrene-treated Golden hamsters but only 1% in the microsomes of phenobarbital-treated hamsters. Thus, we conclude that the high activity of Golden hamster livers towards aflatoxin B1 activation was due presumably to this distinct and unique cytochrome P-450 isozyme which was induced mainly by 3-methylcholanthrene in Golden hamsters.
Fukuhara
M
M
Department of Pharmaceutical Sciences, Institute of Public Health, Tokyo, Japan.
Mizokami
K
K
Sakaguchi
M
M
Niimura
Y
Y
Kato
K
K
Inouye
S
S
Takanaka
A
A
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D015153:Blotting, Western; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D007527:Isoenzymes / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012788:Shrews; D013045:Species Specificity
D000348:Aflatoxins; D007527:Isoenzymes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1