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Carcinogenesis, Vol. 23, No. 5, 861-866, May 2002
© 2002 Oxford University Press

CARCINOGENESIS

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

Luisa Airoldi1, Federica Orsi1, Cinzia Magagnotti1, Renato Coda2, Donato Randone3, Giovanni Casetta4, Marco Peluso5, Agnes Hautefeuille6, Christian Malaveille6 and Paolo Vineis7,,8

1 Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy,
2 Servizio di Anatomia Patologica, Ospedale Gradenigo, Torino, Italy,
3 Servizio di Urologia, Ospedale Gradenigo, Torino, Italy,
4 Cattedra di Patologia Urologica, Università di Torino e Ospedale S. Giovanni Battista, Torino, Italy,
5 Istituto Nazionale Tumori, Genova, Italy,
6 International Agency for Research on Cancer, Lyon, France and
7 Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, via Santena 7, 10126 Torino, Italy

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.


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