| In vitro binding of aflatoxin B1 and 2-acetylaminofluorene to rat, mouse and human hepatocyte DNA: the relationship of DNA binding to carcinogenicity. | |
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MedLine Citation:
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PMID: 3130201 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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DNA binding levels were determined and compared in cultured hepatocytes from male and female rats as well as other animal species following exposure to aflatoxin B1 (AFB1) or 2-acetylaminofluorene (2-AAF). When human, rat (both male and female) and mouse hepatocytes in primary culture were exposed to 2.0 X 10(-7) M [3H]AFB1 (sp. act. 2.63 microCi/nmol) for 24 h, male rat hepatocytes had the highest degree of [3H]AFB1-DNA binding (203 pmol/mg DNA) and human hepatocytes contained the next highest binding level (42 pmol/mg DNA). Hepatocytes from female rats contained 38 pmol/mg DNA while cultured mouse hepatocytes contained only 1.4 pmol/mg DNA. When the same dose of [3H]AFB1 was administered to the cultured male rat hepatocytes at 24 h, 48 h, 72 h and 1 week after seeding, and incubated for 24 h, the DNA binding levels were 189, 175, 76, 75 pmol/mg DNA respectively. In parallel experiments to the cultured male rat hepatocytes above, the AFB1-DNA binding levels in the cultured female hepatocytes were 42, 41, 37 and 34 pmol/mg DNA respectively. Human, male and female rat hepatocytes in primary culture were exposed to 5.2 X 10(-5) M 2-acetylamino[9-14C]fluorene (sp. act. 0.0094 microCi/nmol) for 24 h. It was determined that male rat hepatocytes contained the highest amount of radioactively labeled 2-AAF bound to their DNA (1.57 nmol/mg DNA), female rat hepatocytes contained 0.62 nmol/mg DNA and human hepatocytes contained 0.29 nmol/mg DNA. Results from our in vitro hepatocyte culture system correlate well with in vivo animal studies dealing with species and sex differences in DNA binding and carcinogenic susceptibility. This indicates that hepatocytes in vitro maintain many of the biological properties necessary for carcinogen response similar to liver cells in vivo. In addition, comparison of genotoxic effect in cultured hepatocytes from animals as well as humans may be useful in evaluating carcinogenic potential of xenobiotics in human liver. |
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Authors:
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K E Cole; T W Jones; M M Lipsky; B F Trump; I C Hsu |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Carcinogenesis Volume: 9 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1988 May |
Date Detail:
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Created Date: 1988-06-14 Completed Date: 1988-06-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 711-6 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Maryland School of Medicine, Baltimore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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2-Acetylaminofluorene
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metabolism* Aflatoxin B1 Aflatoxins / metabolism* Animals Cells, Cultured DNA / metabolism* Female Humans Liver / metabolism* Liver Neoplasms / chemically induced* Male Mice Rats Rats, Inbred Strains Sex Factors Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/Aflatoxins; 1162-65-8/Aflatoxin B1; 53-96-3/2-Acetylaminofluorene; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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