The potent carcinogen dibenzo[a,l]pyrene is metabolically activated to fjord-region 11,12-diol 13,14-epoxides in human mammary carcinoma MCF-7 cell cultures

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental hydrocarbon and very potent carcinogen in rodent bioassays, could be activated to DNA-binding intermediates in cells through formation of three different regioisomeric bay- or fjord-region diol-epoxides or other more highly oxidized metabolites. The me...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-02, Vol.54 (4), p.887-890
Main Authors: RALSTON, S. L, LAU, H. H. S, SEIDEL, A, LUCH, A, PLATT, K. L, BAIRD, W. M
Format: Article
Language:English
Subjects:
Benzopyrenes - metabolism
Benzopyrenes - pharmacokinetics
Biological and medical sciences
Biotransformation
Breast Neoplasms - metabolism
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - pharmacokinetics
Chemical agents
DNA - metabolism
Epoxy Compounds - pharmacokinetics
Female
Humans
Medical sciences
Tumor Cells, Cultured
Tumors
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Summary:Dibenzo[a,l]pyrene (DB[a,l]P), an environmental hydrocarbon and very potent carcinogen in rodent bioassays, could be activated to DNA-binding intermediates in cells through formation of three different regioisomeric bay- or fjord-region diol-epoxides or other more highly oxidized metabolites. The mechanism of metabolic activation of DB[a,l]P in the human mammary carcinoma cell line MCF-7 was elucidated by analyzing the DB[a,l]P-DNA adducts formed by [35S]phosphorothioate postlabeling, immobilized boronate chromatography, and high-performance liquid chromatography. Six DB[a,l]P-DNA adducts were detected. Comparison with those formed in cells by DB[a,l]P-11,12-diol and by reaction of DNA with syn- and anti-(benzylic hydroxyl and epoxide oxygen cis and trans, respectively) DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE) demonstrated that all DB[a,l]P-DNA adducts in MCF-7 cells were formed by these diol-epoxide isomers. Cellular DNA contained large amounts of two syn- and one anti-DB[a,l]PDE-DNA adducts and small amounts of one syn- and two anti-DB[a,l]PDE-DNA adducts. The ability of human cells to activate DB-[a,l]P to its fjord-region 11,12-diol 13,14-epoxides suggests that environmental exposure to DB[a,l]P could pose a risk for humans.
ISSN:0008-5472
1538-7445