Journal Article

Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies

Luisa Airoldi, Federica Orsi, Cinzia Magagnotti, Renato Coda, Donato Randone, Giovanni Casetta, Marco Peluso, Agnes Hautefeuille, Christian Malaveille and Paolo Vineis

in Carcinogenesis

Volume 23, issue 5, pages 861-866
Published in print May 2002 | ISSN: 0143-3334
Published online May 2002 | e-ISSN: 1460-2180 | DOI:
Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies

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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/μg DNA for 37/75 patients. Overall the level of adducts was 2.7 ± 0.7 (mean ± SE) fmol/μg DNA (86 ± 22 adducts/108 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.

Keywords: 4-ABP, 4-aminobiphenyl;; CYP1A2, cytochrome P450 1A2;; GC-NICI-MS, gas chromatography-negative ion chemical ionization-mass spectrometry;; NAT, N-acetyltransferase;; OR, odds ratios;; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b-pyridine;; WBC, white blood cells.

Journal Article.  4804 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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