Investigating the effect of dinitrosoamine in stomach cancer
Investigating the effect of dinitrosoamine in stomach cancer
Mohana Kamari,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Globally, there has been a slight drop in both the incidence and mortality rate of stomach cancer in recent decades. It was the third most common cause of cancer-related fatalities globally in 2012, with an estimated 700,000 deaths and over one million new cases of stomach cancer. In Eastern Asia, particularly China, new cases made for about half of the global total. Geographical variations in the prevalence of stomach cancer were noted, suggesting that some modifiable factors may have a significant impact on the etiology of this malignancy. Of the various classes of chemical carcinogens, nitrosamines have probably contributed to a greater extent than most to the understanding of the process of initiation of carcinogenicity. These carcinogens belong to the chemical class of N-nitroso compounds, comprising the N-nitrosamines and the N-nitrosamides. A major difference between the two groups is that the nitrosamides are unstable at physiological pH and decompose nonenzymatically to reactive intermediates; whereas the nitrosamines (eg, dimethylnitrosamine, DMN) are chemically stable under physiological conditions, and their adverse biological effect is mediated through the formation of reactive metabolites after enzymatic conversion, mainly by microsomal mixed-function oxidases. In numerous animal species, the N-nitroso compounds have been proven to be poisonous, teratogenic, mutagenic, and carcinogenic. Additionally, a significant amount of species, tissue, and cell specificity may be shown in the carcinogenic action of these substances, and many of them are carcinogenic. Investigating the role of dinitrosoamine in stomach cancer was the goal of this investigation.
Methods: This study was investigating of Investigating the effect of dinitrosoamine on stomach cancer from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Therefore, it is an urgent demand to identify risk factors that can have a marked impact on this disease. The typical diet in most countries contains nitrates, nitrites, and nitrosamines. Nitrates and nitrites occur naturally in fruit and vegetables, which are regarded as an important part of a healthy diet due to the powerful evidence of beneficial health effects against cancer.
In the same time, nitrates and nitrites are often used as food additives in processed meats such as ham, bacon, sausages, A high consumption of processed meats is linked to an increased gastric cancer risk, and many people consider nitrates/nitrites as the main reason for that. Nitrosamines are produced by chemical reactions of nitrates, nitrites and other proteins. N-nitrosodimethylamine (NDMA) is one of the most frequently occurring nitrosamines in our dietary foods. NDMA is a potent carcinogen, capable of inducing malignant tumors in various animal species in a variety of tissues, including liver, lung, and stomach. A peculiarity of nitrosamines is the high degree of cell and organ specificity in inducing tumors. There is substantial evidence that the initiation of the carcinogenesis process by carcinogens of this group is linked to the metabolic competence of the target tissue or cell to convert these carcinogens into mutagenic metabolites and to the binding of those metabolites to cellular DNA. Alkylation occurs in the DNA at the N-1, N-3, and N-7 positions of adenine; the N-3, N-7, and O6 of guanine; the N-3, and O2 of cytosine; and the N-3, O4, and O2 of thymine; and the phosphate groups. The initial proportion of each DNA adduct depends upon the alkylating agent used.
Conclusion: N-nitroso compounds have been found to be carcinogenic in animal studies.49 Two nitrosamines (N-nitrosodiethylamine and N-nitrosodimethylamine) are classified as probably carcinogenic to humans by the IARC. Epidemiologic studies suggest a positive association between nitrosamines and gastric cancer risk, but the data are still inconclusive. Most epidemiologic investigations on nitrosamine and related food intake and gastric cancer risk have been case-control investigations, which support a positive association of nitrite, nitrosamine, processed meat and fish, preserved vegetables, and smoked food intake with risk for gastric cancer.