Effects of Combined Treatment with Phenolic Compounds and Sodium Nitrite on Two‐stage Carcinogenesis and Cell Proliferation in the Rat Stomach

The effects of combined treatment with NaNO(2) and phenolic compounds on N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) stomach Carcinogenesis were investigated in F344 rats. In the first experiment, groups of 15–20 male rats were treated with an intragastric dose of 150 mg/kg body weight of MNNG, and starting 1 wk later, were given 2.0% butylated hydroxyanisole, 0.8% catechol, 2.0% 3‐methoxycatechol or basal diet either alone or in combination with 0.2% NaNO(2) in the drinking water until they were killed at week 52. All three antioxidants significantly enhanced forestomach Carcinogenesis without any effect of additional NaNO(2) treatment. However, in the absence of MNNG pretreatment, the grade of forestomach hyperplasia in the catechol and 3‐raethoxycatechol groups was significantly increased by the combined treatment with NaNO2. In a second experiment, the combined effects of various phenolic compounds and NaNO(2) on cell proliferation in the upper digestive tract were examined. Groups of 5 rats were given one of 24 phenolic compounds or basal diet either alone or in combination with 0.3% NaNO(2) for 4 weeks and then killed. Particularly strong enhancing effects in terms of thickness of the forestomach mucosa were seen with t‐butylhydroquinone (TBHQ), catechol, gallic acid, 1,2,4‐benzenetriol, dl‐3‐(3,4‐dihydroxyphenyl)‐alanine and hydroquinone in combination with NaNOi. In the glandular stomach, similar enhancing effects were evident in 11 cases, and in the esophagus with phenol, TBHQ and gallic acid. These results demonstrate that NaNO(2) can augment cell proliferation induced in the stomach epithelium by various phenolic compounds.