Abstract |
Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have demonstrated that anti- BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12-dihydrodiols. The DNA adducts formed in these experiments were examined using 32P-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC- DNA adducts formed from both the dihydrodiol- epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a] anthracene and dibenzo[a,l]pyrene.
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Authors | R Agarwal, S L Coffing, W M Baird, A S Kiselyov, R G Harvey, A Dipple |
Journal | Cancer research
(Cancer Res)
Vol. 57
Issue 3
Pg. 415-9
(Feb 01 1997)
ISSN: 0008-5472 [Print] United States |
PMID | 9012467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carcinogens
- Chrysenes
- DNA Adducts
- benzo(g)chrysene
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Topics |
- Biotransformation
- Breast Neoplasms
(metabolism, pathology)
- Carcinogens
(pharmacokinetics)
- Chrysenes
(pharmacokinetics)
- DNA Adducts
(metabolism)
- Female
- Humans
- Tumor Cells, Cultured
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