7-methylguanine and Stomach-Neoplasms

A high gastric cancer mortality in Fujian province (Peoples Republic of China) has been associated with the consumption of certain salted fermented fish products such as fish sauce (FS). We have investigated the levels and nature of N-nitroso compounds (NOC) and genotoxins present, before and after nitrosation, in 49 FS samples collected from villages in this high-risk area, pooled into six samples. The concentrations of total NOC before nitrosation ranged from 0.2 to 16 mumoles/l, and after nitrosation at pH 2 and pH 7, they rose by up to 4800- and 100-fold, respectively. In nitrosated samples, 40-50% of total NOC was not extractable into organic solvents; volatile N nitrosamines accounted for 1-2% and N-nitrosamino acids for 8-16% of total NOC. None of the FS samples exhibited genotoxic activity, but after nitrosation all were weakly active in the SOS chromotest. The highest SOS-inducing potency was observed with nitrosated ethyl acetate extracts of most samples. The formation of methylating agents was measured by incubation of nitrosated FS with DNA and subsequent analysis of 7-methylguanine adduct. 2 of the 6 nitrosated FS samples caused a slight increase in DNA methylation. 1 pooled home-made FS sample (the only one tested) contained tumour promoter-like substances, as measured by expression of certain EBV genes in Raji cells. HPLC fractionation of ethyl acetate extracts of FS samples allowed identification of three UV-absorbing peaks that, upon nitrosation, produced direct-acting genotoxins. This genotoxicity was partly ascribed to the formation of nitrite-derived arene diazonium cations that were characterized by a coupling reaction with N-ethyl-1-naphthylamine and thin-layer chromatography.

Topics: China; Chromatography, High Pressure Liquid; Fermentation; Fish Products; Guanine; Herpesvirus 4, Human; Humans; Hydrogen-Ion Concentration; Methylation; Mutagenicity Tests; Mutagens; Nitrosation; Nitroso Compounds; Risk Factors; SOS Response, Genetics; Stomach Neoplasms

We have measured the urinary excretion of nitrate, N-nitrosoproline, 3-methyladenine and 7-methylguanine in a human population at high risk for gastric cancer. A strong correlation was observed between nitrate and N-nitrosoproline excretion (p less than 0.00000); statistically significant correlations (p less than 0.05) were also observed for N-nitrosoproline with 3-methyladenine (p = 0.003) and with 7-methylguanine (p = 0.03) and for 7-methyl-guanine with nitrate (p = 0.02), although these correlations were sensitive to outliers. Smokers appeared to excrete slightly higher levels of 3-methyladenine than nonsmokers; no other difference was observed between smokers and nonsmokers or between drinkers and nondrinkers. The correlation between N-nitrosoproline excretion and nitrate excretion supports the hypothesis that elevated endogenous nitrate levels may contribute to elevated endogenous formation of N-nitroso compounds.

Topics: Adenine; Guanine; Humans; Nitrates; Nitrosamines; Risk; Stomach Neoplasms

Urinary excretion levels of nitrate and N-nitrosoproline were determined in 160 individuals in a Colombian population at high risk for gastric cancer. In 156 of these subjects urinary levels of 3-methyladenine and 7-methylguanine were determined. Gastric biopsy specimens were obtained from 118 individuals and were histologically characterized according to pathological criteria into the following groups: normal, superficial gastritis, chronic atrophic gastritis, chronic atrophic gastritis with intestinal metaplasia, and dysplastic. The histological changes were correlated with the four variables listed above. There were no significant differences in the excretion of nitrate, N-nitrosoproline, 3-methyladenine, or 7-methylguanine in subjects with different pathological changes. A statistically significant correlation was present between nitrate and N-nitrosoproline excretion in the total population group (r = 0.297, P = 0.0001). A highly significant correlation (r = 0.56, P = 0.0002) was noted for urinary nitrate and N-nitrosoproline excretion in individuals with intestinal metaplasia and dysplasia. An increase in the urinary excretion of 3-methyladenine and 7-methylguanine was associated with tobacco smoking in the total population group.

Topics: Adenine; Colombia; Guanine; Humans; Nitrates; Nitrosamines; Regression Analysis; Risk Factors; Stomach Neoplasms

Topics: Administration, Oral; Animals; Duodenal Neoplasms; Guanine; Jejunal Neoplasms; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach Neoplasms