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ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, Frederick, Maryland 21702 [R. A., A. D.]; Purdue University Cancer Center, West Lafayette, Indiana 47907 [S. L. C., W. M. B.]; and Ben May Institute, Chicago, Illinois 60637 [A. S. K., R. G. H.]
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.
1 Supported in part by the National Cancer Institute, Department of Health and Human Services contract with ABL (R. A., A. D.), and American Cancer Research Grant CN22 (to R. G. H.). The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government.
2 To whom requests for reprints should be addressed, at ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, P. O. Box B, Frederick, MD 21702-1201.
Received 7/ 8/96. Accepted 12/ 3/96.
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