| Effects of benzo[a]pyrene and (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene on mitosis in Chinese hamster V79 cells with stable expression of rat cytochrome P4501A1 or 1A2. | |
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MedLine Citation:
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PMID: 8222063 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effect of bioactivation of benzo[a]pyrene (B[a]P) and (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol) on spindle disturbances and toxicity has been investigated in V79 Chinese hamster cells genetically engineered to express cytochrome P4501A1 (CYP1A1) and cytochrome P4501A2 (CYP1A2). B[a]P induces spindle disturbances in native V79 Chinese hamster cells. This effect was enhanced by the expression of CYP1A1 but not CYP1A2. The increased effect seen in the CYP1A1-expressing cell line could be brought back to the level seen in the native cell line by alpha-naphthoflavone in a dose-dependent manner. This strongly suggests that a CYP1A1-dependent metabolite, conceivably (+-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BPDE) accounts for the increased spindle disturbing effect. B[a]P-7,8-diol induced spindle disturbances at remarkably low concentrations, 10(-8) M, irrespective of expression of the two CYPs. Our data suggest that B[a]P-7,8-diol is the most potent spindle-disturbing metabolite, whereas BPDE is the most important metabolite concerning mutagenesis. The concentrations inducing spindle disturbances correspond to those that are positive in mutation assays. We hypothesize that B[a]P is a complete carcinogen because of its ability to induce both aneuploidy and mutations after metabolic conversion of low non-cytotoxic concentrations. |
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Authors:
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K G Jensen; A Onfelt; H E Poulsen; J Doehmer; S Loft |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Carcinogenesis Volume: 14 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1993 Oct |
Date Detail:
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Created Date: 1993-12-01 Completed Date: 1993-12-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2115-8 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Copenhagen, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzo(a)pyrene / metabolism, pharmacology* Benzoflavones / pharmacology Cell Line Cell Survival / drug effects Cricetinae Cricetulus Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A2 Cytochrome P-450 Enzyme System / genetics, metabolism* Dihydroxydihydrobenzopyrenes / metabolism, pharmacology* Mitosis* Oxidoreductases / genetics, metabolism* Rats Transfection |
| Chemical | |
Reg. No./Substance:
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0/Benzoflavones; 0/Dihydroxydihydrobenzopyrenes; 13345-25-0/benzo(a)pyrene 7,8-dihydrodiol; 50-32-8/Benzo(a)pyrene; 604-59-1/alpha-naphthoflavone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/Cytochrome P-450 CYP1A2 |
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