6533b7d5fe1ef96bd1263b0c

RESEARCH PRODUCT

Stereoselective Metabolic Activation of Dibenzo[a,l]Pyrene in the Human Mammary Carcinoma Cell Line MCF-7 Results in Formation of (-)-antiand (+)-syn-11,12-Diol-13,14-Epoxidedeoxyadenosine Adducts in DNA

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Abstract Dibenzo[a,l]pyrene (DB[a,l]P) is an important polycyclic aromatic hydrocarbon because of possible human exposure and its exceptionally high carcinogenicity in rodents. We examined the metabolism of DB[a,l]P and the formation of DB[a,l]P-DNA adducts in the human mammary carcinoma cell line (MCF-7). Analysis of the DNA adducts by 33P-postlabeling, immobilized boronate chromatography, HPLC and TLC demonstrated that DB[a,l]P is stereoselectively metabolized to specific optical isomers of DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE). The major anti-DB[a,l]PDE adduct formed in DB[a,l]P-treated MCF-7 cells resulted from reaction of (-)-anti-DB[a,l]PDE with DNA whereas the two major syn-DB[a,l]PDE adducts resulted from (+)-syn-DB[a,l]PDE. All three major adducts were with deoxyadenosine, but small amounts of deoxyguanosine adducts were also detected. These results indicate that DB[a,l]P is metabolized to both the (+)- and (-)-11,12-dihydrodiols and that the (-)-dihydrodiol is stereoselectively activate...