Document Detail

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.
MedLine Citation:
PMID:  8222063     Owner:  NLM     Status:  MEDLINE    
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.
K G Jensen; A Onfelt; H E Poulsen; J Doehmer; S Loft
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  14     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1993-12-01     Completed Date:  1993-12-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2115-8     Citation Subset:  IM    
Department of Pharmacology, University of Copenhagen, Denmark.
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MeSH Terms
Benzo(a)pyrene / metabolism,  pharmacology*
Benzoflavones / pharmacology
Cell Line
Cell Survival / drug effects
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2
Cytochrome P-450 Enzyme System / genetics,  metabolism*
Dihydroxydihydrobenzopyrenes / metabolism,  pharmacology*
Oxidoreductases / genetics,  metabolism*
Reg. No./Substance:
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 P-450 CYP1A1; EC P-450 CYP1A2

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