Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies
Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies
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DOI：
10.1093/carcin/23.5.861
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发表时间：
2002-05-01
期刊：
影响因子：
4.7
通讯作者：
Vineis, P
中科院分区：
文献类型：
--
作者：
Airoldi, L;Orsi, F;Vineis, P
暴露于4-氨基联苯（4-ABP）是人类膀胱癌的重要决定因素。我们用气相色谱-质谱法分析了75例膀胱癌活检标本中4-ABP的DNA加合物。目的是了解是否吸烟，N-乙酰转移酶2（NAT 2）多态性，饮食或肿瘤分级的决定因素4-ABP-DNA水平。75例患者中有37例的4-ABP-DNA加合物高于0.1 fmol/ mug DNA的检测限。总的来说，加合物水平为2.7 +/- 0.7（平均值+/- SE）fmol/mug DNA（86 +/- 22个加合物/10（8）个正常核苷酸，平均值+/- SE）。观察到与等级的强关联。在可检测到4-ABP-DNA加合物的患者组中，与1级相比，2级或3级肿瘤的比值比分别为4.3（95% CI 0.8-21.9）和6（1.3-27.5）。在2级和3级中，发现加合物水平与推断的慢乙酰化表型之间存在非统计学显著相关性。水果和蔬菜的摄入量产生的可检测加合物的频率较低，尽管这种关联在统计学上并不显著。可检测到的4-ABP-DNA加合物与较高肿瘤级别（3级与1 + 2级，比值比10.4; 95% CI 1.7-63.1）的当前吸烟明显相关。总的来说，我们的研究结果表明，更高水平的DNA加合物表征更具侵袭性的肿瘤（更高的肿瘤等级）。这似乎是促进吸烟和对比的水果和蔬菜的摄入量。
Exposure to 4-aminobiphenyi (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/ mug DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/mug 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.