Romano G, Garagnani L, Boninsegna A, Ferrari P, Flamini G, De Gaetani C, Sgambato A, Giovanni F, Curigliano G, Ferretti G, Cittadini A, Trentini G
Giovanni XXIII Research Cancer Center, Institute of General Pathology, Catholic University School of Medicine, Rome, Italy.
Anticancer Res. 1999 Sep-Oct;19(5C):4571-6.
Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms.
(4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients.
4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence.
These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.
4-氨基联苯（4-ABP）的活化中间体能够与DNA发生共价相互作用形成加合物。有大量证据表明致癌物-DNA加合物的形成可能是癌症起始机制之一。
在106例膀胱尿路上皮癌患者的标本中评估了（4-ABP）诱导的DNA损伤与p53过表达及突变的情况。
与不吸烟者相比，吸烟者的4-ABP-DNA加合物水平更高，具有临界统计学意义。p53核过表达与肿瘤分级相关，而与分期、4-ABP-DNA加合物、吸烟习惯和疾病复发均无显著相关性。关于分子分析，106例中有17例（16%）发现p53点突变，突变模式与更高的分级和分期均显著相关，但与疾病复发无关。
这些结果表明，除烟草烟雾外，其他来源可能也会导致膀胱组织中4-ABP-DNA加合物的形成，并且p53表达/突变不能被视为膀胱癌的预后因素。
