Abstract

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.