Lu S H, Montesano R, Zhang M S, Feng L, Luo F J, Chui S X, Umbenhauer D, Saffhill R, Rajewsky M F
J Cell Physiol Suppl. 1986;4:51-8. doi: 10.1002/jcp.1041290411.
Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.
本文综述了中国关于N-亚硝胺与食管癌相关性的研究。食管癌是一个复杂的多因素问题。尽管在中国，亚硝胺暴露与食管癌之间的因果关系尚未得到严格证实，但在我们的研究中，已检测到林县居民直接接触亚硝胺或其体内形成亚硝胺的情况。从林县居民收集的胃液中已检测出几种N-亚硝胺（NDMA、NDEA、NMBzA、NPyr、NPip和NSAR）。发现食管上皮病变与亚硝胺含量之间存在相关性。此外，林县居民24小时尿液中排泄的N-亚硝基氨基酸（N-亚硝基脯氨酸、N-亚硝基噻唑烷-4-羧酸、NSAR和硝酸盐）含量显著高于范县居民，这表明高危地区居民对N-亚硝基化合物及其前体的暴露程度更高。已在细胞水平上研究了亚硝胺对人体食管的影响。林县患者食管或胃黏膜DNA中O6-MedG的含量高于欧洲（里昂和埃森）患者。在用NMBzA培养的人胎儿食管中也检测到了O6-MedG的存在。这些发现表明，食管DNA中O6-MedG水平升高可能是近期接触N-亚硝基化合物的结果，或者是基因决定的细胞修复DNA中O6-MedG能力降低的结果。在用NMBzA培养2周至2个月的人胎儿食管中诱导出了增生。已开展林县食管癌的干预研究。林县居民摄入适量的抗坏血酸可有效将N-亚硝基氨基酸的尿液水平降低至低危地区未服用者的水平。如果N-亚硝基化合物在体内形成且是林县食管癌的致病因素之一，抗坏血酸似乎可有效降低这些致癌化合物的身体负担。因此，林县开展了化学预防计划。
