title: Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies.
abstract: 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.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Airoldi
authors.forename: Federica
authors.initials: F
authors.lastname: Orsi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Magagnotti
authors.forename: Renato
authors.initials: R
authors.lastname: Coda
authors.forename: Donato
authors.initials: D
authors.lastname: Randone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casetta
authors.forename: Marco
authors.initials: M
authors.lastname: Peluso
authors.forename: Agnes
authors.initials: A
authors.lastname: Hautefeuille
authors.forename: Christian
authors.initials: C
authors.lastname: Malaveille
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D000328:Adult; D000368:Aged; D000611:Aminobiphenyl Compounds / Q000494:pharmacology*; D001706:Biopsy; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; C006757:4-biphenylamine; D004247:DNA