P53 MUTATIONS AT A-T BASE-PAIRS IN ANGIOSARCOMAS OF VINYL CHLORIDE-EXPOSED FACTORY-WORKERS
P53 MUTATIONS AT A-T BASE-PAIRS IN ANGIOSARCOMAS OF VINYL CHLORIDE-EXPOSED FACTORY-WORKERS
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DOI：
10.1093/carcin/15.1.1
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发表时间：
1994-01-01
期刊：
影响因子：
4.7
通讯作者：
MONTESANO, R
中科院分区：
文献类型：
--
作者：
HOLLSTEIN, M;MARION, MJ;MONTESANO, R
p53 肿瘤抑制基因突变常见于主要人类癌症中，某些癌症类型的突变谱与相关环境危险因素的基因毒性作用一致。迄今为止，关于有工作场所致癌物接触史的工厂工人患癌症的 p53 突变的信息还很少。职业接触氯乙烯会导致肝血管肉瘤 (ASL)，还会增加患几种其他癌症的风险。骨肉瘤和纤维肉瘤中 p53 功能的丧失可能通过两种不同的机制发生：p53 突变和 MDM2 基因扩增。我们检查了 5 名接触氯乙烯的患者（其中 4 名患有 ASL，1 名患有肝细胞癌 (HCC)）的肿瘤，以寻找 MDM2 原癌基因扩增或外显子 5-8 中 p53 突变的证据。未发现 MDM2 扩增，但在两个血管肉瘤中检测到 A:T 至 T:A 错义突变。氯乙烯相关癌症的 p53 序列分析可能为致癌物暴露与癌症相关基因 DNA 损伤之间的关系提供有价值的信息。
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 envirommental 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.