Pfohl-Leszkowicz A, Grosse Y, Carrière V, Cugnenc P H, Berger A, Carnot F, Beaune P, de Waziers I
Ecole Nationale Supérieure Agronomique de Toulouse, Laboratoire de Toxicologie et Sécurié Alimentaire, France.
Cancer Res. 1995 Dec 1;55(23):5611-6.
Colon cancer is one of the most frequent causes of cancer death in western countries. Epidemiological studies suggest that colorectal cancer can be attributed, at least in part, to carcinogens and mutagens present in the diet and/or the environment. The covalent binding of these xenobiotics or their reactive metabolites to DNA is believed to initiate this chemical carcinogenesis. In the present study, using a 32P-postlabeling method, we investigated DNA adduct levels in control colons from patients without colorectal adenocarcinoma and in nontumoral and tumoral tissues from patients with colorectal adenocarcinoma. Our results show that the DNA adduct level is significantly higher (P < 0.001) in nontumoral than in control or tumoral colon samples. For the first time, we demonstrate in humans that the presence of numerous adducts in colonic mucosa is associated with colorectal cancer, a finding in agreement with the importance of chemical factors in causing this disease; therefore, after confirmation of the link between DNA adducts and colorectal cancer, the measurement of DNA adduct levels in colon samples could constitute a useful approach to the early detection of colorectal cancer.
在西方国家，结肠癌是癌症死亡的最常见原因之一。流行病学研究表明，结直肠癌至少部分可归因于饮食和/或环境中存在的致癌物和诱变剂。这些外源性物质或其活性代谢产物与DNA的共价结合被认为启动了这种化学致癌过程。在本研究中，我们使用32P后标记法，调查了无结直肠腺癌患者的对照结肠以及结直肠腺癌患者的非肿瘤组织和肿瘤组织中的DNA加合物水平。我们的结果表明，非肿瘤结肠样本中的DNA加合物水平显著高于对照或肿瘤结肠样本（P < 0.001）。我们首次在人类中证明，结肠黏膜中存在大量加合物与结直肠癌有关，这一发现与化学因素在引发该疾病中的重要性相符；因此，在证实DNA加合物与结直肠癌之间的联系后，测量结肠样本中的DNA加合物水平可能成为早期检测结直肠癌的一种有用方法。
