| Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s. | |
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MedLine Citation:
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PMID: 2126562 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome P-450 isozymes, P-450 MC1 (IIA) and P-450 MC4 (IA2), were purified from 3-methylcholanthrene-treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P-450 MC1 and P-450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P-450s specifically inhibited these activities. Antibody against P-450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3-methyl-cholanthrene-treated hamster liver microsomes. In contrast, antibody against P-450 MC4 stimulated the activity by 175%. These results indicated that hamster P-450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P-450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P-450 MC1 and MC4 were genotoxic in the umu mutagen test. |
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Authors:
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T S Lai; J Y Chiang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of biochemical toxicology Volume: 5 ISSN: 0887-2082 ISO Abbreviation: J. Biochem. Toxicol. Publication Date: 1990 |
Date Detail:
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Created Date: 1991-03-19 Completed Date: 1991-03-19 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8700114 Medline TA: J Biochem Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 147-53 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, Rootstown 44272. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aflatoxin B1 Aflatoxins / immunology, metabolism* Animals Antibodies / immunology Cricetinae Cytochrome P-450 Enzyme System / biosynthesis, isolation & purification, metabolism* Enzyme Induction / drug effects Gene Expression Regulation, Enzymologic Liver / drug effects, enzymology* Mesocricetus Methylcholanthrene / pharmacology* Microsomes, Liver / enzymology Mutagenicity Tests Rats Rats, Inbred Strains Salmonella typhimurium / enzymology, genetics Subcellular Fractions / drug effects, enzymology |
| Grant Support | |
ID/Acronym/Agency:
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GM31584/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aflatoxins; 0/Antibodies; 1162-65-8/Aflatoxin B1; 56-49-5/Methylcholanthrene; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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