Hollstein M, Marion M J, Lehman T, Welsh J, Harris C C, Martel-Planche G, Kusters I, Montesano R
IARC, Lyon, France.
Carcinogenesis. 1994 Jan;15(1):1-3. doi: 10.1093/carcin/15.1.1.
Mutations in the p53 tumor suppressor gene are commonly found in the major human cancers and the mutational spectrum in some cancer types is consistent with the genotoxic effects of the associated environmental risk factors. Thus far there is little information on p53 mutations in cancers of factory workers with a history of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride causes liver angiosarcomas (ASL) and also increases the risk of several other cancers. Loss of p53 function in osteo- and fibrosarcomas can occur by two different mechanisms, p53 mutation and amplification of the MDM2 gene. We examined tumors from five vinyl chloride-exposed patients, four with ASL and one with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene amplification or p53 mutation in exons 5-8. Amplification of MDM2 was not found, but in two of the angiosarcomas an A:T to T:A missense mutation was detected. p53 sequence analysis of vinyl chloride associated cancers may provide valuable information on the relationship between carcinogen exposure and DNA damage in cancer-related genes.
p53肿瘤抑制基因的突变在主要人类癌症中普遍存在，并且某些癌症类型中的突变谱与相关环境风险因素的遗传毒性效应一致。到目前为止，关于有工作场所致癌物暴露史的工厂工人癌症中p53突变的信息很少。职业性接触氯乙烯会导致肝血管肉瘤（ASL），还会增加患其他几种癌症的风险。骨肉瘤和纤维肉瘤中p53功能的丧失可通过两种不同机制发生，即p53突变和MDM2基因扩增。我们检查了5名接触氯乙烯患者的肿瘤，其中4例为ASL，1例为肝细胞癌（HCC），以寻找外显子5-8中MDM2原癌基因扩增或p53突变的证据。未发现MDM2扩增，但在两例血管肉瘤中检测到A:T到T:A的错义突变。对氯乙烯相关癌症进行p53序列分析可能会提供有关致癌物暴露与癌症相关基因中DNA损伤之间关系的有价值信息。
