Carcinogen-DNA Adducts in Exfoliated Urothelial Cells: Techniques for Noninvasive Human Monitoring

Abstract

Detection of carcinogen-DNA adducts in DNA from exfoliated urothelial cells from animals and humans exposed to potential environmental carcinogens is described. In an animal model, 4-aminobiphenyl-DNA adducts were detected, and the shape of the dose-response curve was related to the levels of 4-aminobiphenyl-hemoglobin adducts. In a human study, five distinct adducts were two to nine times higher in smokers than in nonsmokers. The association of four adduct measures with smoking was corroborated by significant correlations with levels of 4-aminobiphenyl-hemoglobin adducts, type and number of cigarettes smoked, and/or urinary mutagenicity. One adduct seemed chromatographically similar to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. This adduct showed the strongest correlation with 4-aminobiphenyl-hemoglobin adduct levels. These data suggest that noninvasive techniques can be applied to the study of carcinogen-DNA adducts in the target organ of humans at risk for urinary bladder cancer.