W. Baird, Sherry L. Ralston, A. Luch
Nov 1, 1996
Citations
0
Influential Citations
5
Citations
Quality indicators
Journal
Polycyclic Aromatic Compounds
Abstract
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...