Exposure to
4-aminobiphenyl (4-ABP) is an important determinant of
urinary bladder cancer in humans. We have analyzed by gas chromatography-mass spectrometry the
DNA adducts of 4-ABP in 75
bladder cancer biopsies. The purpose was to understand whether smoking, N-
acetyltransferase 2 (NAT2) polymorphism, diet or
tumor grade were determinants of 4-ABP-DNA levels. 4-ABP-DNA adducts were above the detection limit of 0.1 fmol/microg
DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/microg
DNA (86 +/- 22 adducts/10(8) normal
nucleotides, mean +/- SE). A strong association with grade was observed. In the group of patients with detectable 4-ABP-DNA adducts the odds ratio for having a
tumor grade of 2 or 3 was respectively 4.3 (95% CI 0.8-21.9) and 6 (1.3-27.5), compared with grade 1. A non-statistically significant association was found between adduct levels and the deduced slow acetylator phenotype in grades 2 and 3. The intake of fruit and vegetables produced a lower frequency of detectable adducts, though the association was not statistically significant. Detectable 4-ABP-DNA adducts were clearly associated with current smoking in higher
tumor grades (grade 3 versus grades 1 + 2, odds ratios 10.4; 95% CI 1.7-63.1). Overall, our findings indicate that higher levels of
DNA adducts characterize more invasive
tumors (higher
tumor grades). This seems to be facilitated by smoking and contrasted by the intake of fruit and vegetables.