Metabolism of 7,12-dimethylbenz(a)anthracene and its DNA adduct formation in human fetal kidney and intestinal cells in culture.

Epithelial cell cultures derived from human fetal intestine and kidney were analyzed for their capability to metabolize 7,12-dimethylbenz(a)anthracene (DMBA) and form DNA-DMBA adducts. Both the intestinal and kidney cells were able to metabolize DMBA to water and organic soluble metabolites and formed DMBA-DNA adducts. Intestinal cells metabolized 39.5 +/- 25.2% of the DMBA to organic soluble products and 2.9 +/- 0.4% to water-soluble metabolites after 24-hr incubation. Kidney cells yielded 27.4 +/- 18.1 and 3.8 +/- 2.7% organic and water-soluble metabolites, respectively. Kidney cells appeared to produced larger amounts of 7,12-dihydroxymethylbenz(a)anthracene and DMBA-8,9-dihydrodiols than intestinal cell cultures, while intestinal cells produced greater amounts of phenol metabolites. The level of DNA-DMBA adducts formed in the intestinal and kidney cell cultures after 24-hr incubation were 20.4 +/- 17.1 and 36.7 +/- 25.3 mumol DMBA/mol DNA-phosphate, respectively. Major elution peaks were observed where the DMBA-1,2-epoxide-3,4-dihydrodiol-deoxyguanosine adduct eluted. These data indicate qualitatively similar, but quantitatively different, levels of DMBA metabolites and DMBA-DNA adducts produced by human fetal intestinal and kidney epithelial cells in culture.