Li H, Lu S, Cui X
Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
Zhonghua Zhong Liu Za Zhi. 1995 May;17(3):170-4.
Results of epidemiological studies have shown that nitrosamine-induced carcinogensis is involved in esophageal cancer in China. In order to demonstrate the mechanism at molecular level, Multiple tumor suppressor genes Rb, p53, APC and MCC in human fetus esophageal epithelium treated with NMBzA (in vitro) for 24 hours or three weeks and esophageal carcinoma induced by NMBzA were analyzed with PCR amplification and direct sequencing. In PCR amplification analysis. Rb, p53, APC and MCC deletions in esophageal carcinoma of human fetus induced by NMBzA were found, but no deletions of these genes was demonstrated in NMBzA-treated human fetal esophageal epithelium. PCR direct sequencing analysis revealed mutation of p53, Rb and MCC genes in human fetal esophageal epithelium treated with NMBzA for three weeks. The results first confirmed (in vitro) that nitrosamine can cause mutations and deletions of multiple tumor suppressor genes in human esophageal epithelium. The mutations of tumor suppressor genes in nitrosamine-induced esophageal carcinoma may occur in the early stage, while deletions in late stage of carcinogenesis.
流行病学研究结果表明，亚硝胺诱导的致癌作用与中国的食管癌有关。为了在分子水平上阐明其机制，采用PCR扩增和直接测序方法，对用NMBzA（体外）处理24小时或三周的人胎儿食管上皮以及由NMBzA诱导的食管癌中的多个肿瘤抑制基因Rb、p53、APC和MCC进行了分析。在PCR扩增分析中，发现NMBzA诱导的人胎儿食管癌中有Rb、p53、APC和MCC缺失，但在NMBzA处理的人胎儿食管上皮中未显示这些基因的缺失。PCR直接测序分析显示，用NMBzA处理三周的人胎儿食管上皮中p53、Rb和MCC基因发生了突变。这些结果首次（在体外）证实亚硝胺可导致人食管上皮中多个肿瘤抑制基因发生突变和缺失。亚硝胺诱导的食管癌中肿瘤抑制基因的突变可能发生在癌变早期，而缺失则发生在癌变后期。
