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Relevance of N‐nitrosamines to esophageal cancer in China
Author(s) -
ShihHsin Lu,
Montesano Ruggero,
MingShu Zhang,
Luo Feng,
FengJi Luo,
ShaoXing Chui,
Umbenhauer Diena,
Saffhill R.,
Rajewsky M. F.
Publication year - 1986
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041290411
Subject(s) - esophagus , esophageal cancer , nitrosamine , gastroenterology , nitrosation , carcinogen , cancer , pepsin , urine , medicine , chemistry , physiology , biochemistry , enzyme
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 O 6 ‐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 O 6 ‐MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O 6 ‐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 O 6 ‐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 pursured. Intake of moderate doses of ascorbic acids by Lin‐Xian subjects effectively reduced the urinary levels of N‐nitrosamino acids to those found in undosed 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.