Metabolism of benzo(a)pyrene by human epithelial and fibroblastic cells: metabolite patterns and DNA adduct formation.
We demonstrate in cell culture that mammary epithelial cells from normal human breast specimens metabolize benzo(a)pyrene (BaP) and form adducts with the bases of their DNA more readily and at lower concentrations of BaP than do fibroblasts from the same specimens. BaP metabolism and adduct formation was determined in the same incubations with epithelial cells grown out in early passage from each of three specimens and with fibroblasts from one of these specimens. The metabolite pattern of the epithelial cells was indicative of preferential formation of 7, 8-dihydrodiol-9, 10-dihydroepoxybenzo(a)pyrene the ultimate carcinogen. In contrast, fibroblasts formed mainly mono- and dihydroxide derivatives of BaP. The metabolite pattern from epithelial cells was compatible with the ease in which adducts between DNA and the diolepoxide of benzo(a)pyrene were formed. These results provide evidence that chemical carcinogens should be considered as possible factors in the induction of breast cancer in women.
D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D001940:Breast; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D004247:DNA