Stereoselective activation of dibenzo[a,l]pyrene to (-)-anti (11R,12S,13S,14R)- and (+)-syn(11S,12R,13S,14R)-11,12-diol-13,14-epoxides which bind extensively to deoxyadenosine residues of DNA in the human mammary carcinoma cell line MCF-7

Carcinogenesis
S L RalstonW M Baird

Abstract

Dibenzo[a,l]pyrene (DB[a,l]P) is an environmental contaminant and a very potent carcinogen. DB[a,l]P exceeds the carcinogenic potency of both benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in rodent bioassays. Previous studies demonstrated that DB[a,l]P is metabolized to DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE) in the human mammary carcinoma cell line MCF-7. In the present study the major DNA adducts formed in DB[a,l]P-treated MCF-7 cells have been identified through the use of 33P-postlabeling. TLC and HPLC. DB[a,l]P is metabolically activated in MCF-7 cells to form large amounts of three major DNA adducts and smaller amounts of three other adducts. The three major DNA adducts are with deoxyadenosine: two are formed by reaction of (+)-syn-DB[a,l]PDE (11S,12R,13S,14R), the third by reaction of (-)-anti-DB[a,l]PDE (11R,12S,13S,14R). The results demonstrate that DB[a,l] is stereoselectively metabolized in MCF-7 cells to form one enantiomer of each diol epoxide diastereomer; (+)-syn-DB[a,l]PDE and (-)-anti-DB[a,l]PDE. The high extent of binding of these diol epoxides to deoxyadenosine in DNA of MCF-7 cells may help to explain the very high carcinogenic potency of DB[a,l]P and suggests that DB[a,l]P could also pose a carci...Continue Reading

Citations

Jul 12, 2007·Journal of Biochemical and Molecular Toxicology·Brinda MahadevanWilliam M Baird
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·V J Melendez-ColonW M Baird
Sep 16, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tamara Musafia-JeknicWilliam M Baird
Jul 11, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kristine C OlsonPhilip Lazarus
Dec 26, 2006·International Journal of Cancer. Journal International Du Cancer·Brinda MahadevanWilliam M Baird
Jun 2, 2011·Organic & Biomolecular Chemistry·Kunduchi P VijayalakshmiCherumuttathu H Suresh
Mar 29, 2002·Environmental and Molecular Mutagenesis·Donghui LiJohn DiGiovanni
Jan 10, 2001·International Journal of Cancer. Journal International Du Cancer·W A SmithR C Gupta
Oct 25, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lauren A CourterWilliam M Baird
Jun 21, 2005·Toxicology and Applied Pharmacology·Weiling Xue, David Warshawsky

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