Progress of gastric cancer etiology: N-nitrosamides 1999s.

Abstract

Stomach carcinoma is still the leading cause of cancer death in China and the second one in the world. Its possible causes include: (1) chemical factors such as intragastric formation of N-nitroso compounds (NOC) and high salt intake; (2) biological factors such as infection of Helicobacter pylori and biotoxins intake; and (3) nutritional factors such as deficiency of vitamin C, selenium, and other antioxidants. Nitrogenous precursors of NOC, e.g. alkylamines, alkylur eas, alkylguanidines, and alkylamides, occur widely in nature and potential nitrosating agents, e.g., nitrite (NO2-) and NOx (the gaseous oxides of nitrogen) are similarly widespread. Relationship between exposure to NOC and causes of human cancer was investigated extensively ten years ago. Resu lts indicated that the exposures of NOC might contribute to the occurrences of m alignancy in the upper digestive tracts including stomachs. It was also observed that both high salt intake and deficiency of some micronutrients enhanced NOC- induced carcinogenicity. Recent studies show that infection of H. pylori can lead to atrophic gastritis and achlorhydria, and promote endogenous formation of NOC indirectly[1]. Much attention has been paid to stomach cancer and NOC regarding the characterization of natural N-nitrosamides in human environment in the 1990s. N-nitrosamides, one kind of direct-acting NOC, can be synthesized endogenously in stomach lumens and damaged DNA of gastric mucosal epithelium in situ. Most of epidemiological investigations showed that the occurrence of stomach cancers was correlated positively with exposure levels of nitrosating agents and ni trogenous precursors of NOC[2]. Laboratory synthesized N-nitrosamides are strong animal stomach carcinogens. Intragastric N-nitrosamide formation may play an important role in the etiology of gastric carcinomas[3]. However, most N-nitrosamides are chemically reactive, thermal, photo, and alkali-labile compounds. It is very difficult to detect N-nitrosamid es in human environments chemically. Little was known about the existence of n atu ral N-nitrosamides before the 1980s because of lack of a convenient sensi tive method to detect them precisely[4]. Several progresses have been ma de on the study of N-nitrosamides in the past ten years, including setup of detection meth ods for trace N-nitrosamides in the early 1990s[5,6] resulting in recent discovery of natural N-nitrosoureas in human environments[7-9]. This article will present and discuss results of studies on stomach cancer and N-nitrosamides in the past decade.