Lu S H, Chui S X, Yang W X, Hu X N, Guo L P, Li F M
Cancer Institute, Chinese Academy of Medical Sciences, Beijing.
IARC Sci Publ. 1991(105):11-7.
Oesophageal cancer occurs at a very high frequency in certain areas of China, especially in Linxian county, Henan province. Previous studies suggested that N-nitroso compounds play a causative role. In order to study further the exposure of Linxian inhabitants, the intake of N-nitrosamines in the diet was determined. The total daily intake of volatile nitrosamines and of N-nitroso-N-methylbenzylamine (NMBzA) was higher in Linxian than in two other counties. NMBzA can induce cancer in animal and human oesophageal epithelium. Human fetal oesophageal epithelia were cultured with NMBzA for 4 h, and eight monkeys were treated with NMBzA. High-molecular-weight DNA extracted from explants and from the oesophageal epithelia of monkeys induced malignant transformation of NIH 3T3 cells. Alu and monkey-specific repeat sequences were present in transformed cells, and H-ras was found in the transforming DNA. Human fetal oesophageal epithelium cultured with NMBzA was transplanted into the mesentery of BALB/c nude mice. Tumours were found after eight months; and the Alu sequence was present in DNA extracted from tumours induced by NMBzA, showing that the tumours were of human origin. The results provide direct evidence that NMBzA is carcinogenic in human oesophageal epithelium and that N-nitrosamines are one of the causative factors of oesophageal cancer in Linxian county.
食管癌在中国某些地区，尤其是河南省林县的发病率极高。以往研究表明，N-亚硝基化合物起到致病作用。为了进一步研究林县居民的暴露情况，对饮食中N-亚硝胺的摄入量进行了测定。林县居民每天摄入的挥发性亚硝胺和N-亚硝基-N-甲基苄胺（NMBzA）总量高于其他两个县。NMBzA可在动物和人类食管上皮中诱发癌症。将人胎儿食管上皮与NMBzA培养4小时，并对8只猴子用NMBzA进行处理。从外植体和猴子食管上皮中提取的高分子量DNA诱导NIH 3T3细胞发生恶性转化。转化细胞中存在Alu序列和猴子特异性重复序列，并且在转化DNA中发现了H-ras。将用NMBzA培养的人胎儿食管上皮移植到BALB/c裸鼠的肠系膜中。八个月后发现了肿瘤；并且在从NMBzA诱导的肿瘤中提取的DNA中存在Alu序列，表明这些肿瘤起源于人类。这些结果提供了直接证据，证明NMBzA对人类食管上皮具有致癌性，并且N-亚硝胺是林县食管癌的致病因素之一。
