sodium-nitrite and catechol

To clarify the mechanisms underlying forestomach carcinogenesis in rats by co-treatment with catechol and sodium nitrite (NaNO2), we investigated the involvement of oxidative stress resulting from reaction of the two compounds. Since generation of semiquinone radical, hydroxyl radical (*OH), and peroxynitrite (ONOO-) arose through the reaction of catechol with NO, we proposed that superoxide resulting from catechol oxidation reacted with excess NO, consequently yielding *OH via ONOO-. Male F344 rats were co-treated with 0.2% catechol in the diet and 0.8% NaNO2 in the drinking water for 2 weeks. Prior to occurrence of histological evidence indicating epithelial injury and hyperplasia, 8-hydroxydeoxyguanosine levels in forestomach epithelium significantly increased from 12 h together with appearance of immunohistochemically nitrotyrosine-positive epithelial cells. There were no remarkable changes in rats given each chemical alone. We conclude that oxidative stress due to NO plays an important role in induction of forestomach epithelial damage, cell proliferation, and thus presumably forestomach carcinogenesis.

Topics: Administration, Oral; Animals; Catechols; Cell Proliferation; Drug Combinations; Gastric Mucosa; Male; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach; Stomach Neoplasms

The effects of combined treatment with NaNO2 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% NaNO2 in the drinking water until they were killed at week 52. All three antioxidants significantly enhanced forestomach carcinogenesis without any effect of additional NaNO2 treatment. However, in the absence of MNNG pretreatment, the grade of forestomach hyperplasia in the catechol and 3-methoxycatechol groups was significantly increased by the combined treatment with NaNO2. In a second experiment, the combined effects of various phenolic compounds and NaNO2 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% NaNO2 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 NaNO2. 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 NaNO2 can augment cell proliferation induced in the stomach epithelium by various phenolic compounds.

Topics: Animals; Butylated Hydroxyanisole; Carcinoma, Squamous Cell; Catechols; Cell Division; Hyperplasia; Male; Methylnitronitrosoguanidine; Phenols; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach; Stomach Neoplasms

Effects of simultaneous treatment with NaNO2 and butylated hydroxyanisole, catechol, or 3-methoxycatechol were examined in a rat multiorgan carcinogenesis model. Groups of 15 animals were given a single i.p. injection of 100 mg/kg of body weight diethylnitrosamine, 4 i.p. injections of 20 mg/kg of body weight N-methylnitrosourea, 4 s.c. injections of 40 mg/kg of body weight dimethylhydrazine, p.o. treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for the first 2 weeks and p.o. treatment with 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine in the drinking water for the next 2 weeks of the initial 4-week initiation period. Starting 3 days after the completion of these carcinogen treatments, animals were given diets containing 2% butylated hydroxyanisole, 0.8% catechol, 2% 3-methoxycatechol, or basal diet either alone or in combination with 0.3% sodium nitrite until week 28, when complete autopsy was performed. Histological examination showed that NaNO2 strongly enhanced development of forestomach lesions but inhibited that of glandular stomach lesions in rats simultaneously given catechol or 3-methoxycatechol with or without prior carcinogen exposure. 3-Methoxycatechol promoted esophageal carcinogenesis either with or without NaNO2, but promoting effects of catechol were evident only in the presence of NaNO2. In addition, treatment with NaNO2 after carcinogen exposure enhanced forestomach carcinogenesis. These results indicate that NaNO2 can modify phenolic antioxidant-induced cell proliferation and/or carcinogenesis, particularly in the upper digestive tract.

Topics: Animals; Antioxidants; Body Weight; Butylated Hydroxyanisole; Carcinoma in Situ; Carcinoma, Squamous Cell; Catechols; Cocarcinogenesis; Dimethylhydrazines; Disease Models, Animal; Drug Interactions; Eating; Epithelium; Hyperplasia; Liver; Male; Methylnitrosourea; Neoplasms, Experimental; Organ Size; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach; Stomach Neoplasms

The effects of sodium nitrite (NaNO2) and catechol or 3-methoxycatechol in combination were examined in male F344 rats. Animals were treated with 0.3% NaNO2 in the drinking water and 0.8% catechol or 2% 3-methoxycatechol in powdered diet for 24 weeks. While catechol or 3-methoxycatechol alone induced low incidences of mild or moderate hyperplasia, simultaneous administration of NaNO2 markedly enhanced the degree of hyperplasia and papilloma formation. In contrast, induction of submucosal hyperplasia and adenomas in the glandular epithelium was reduced. Thus, the results indicate that NaNO2 can modulate the metabolism of antioxidants, so that, possibly via production of new active moieties, targeting of forestomach epithelium is enhanced.

Topics: Adenoma; Animals; Antioxidants; Body Weight; Catechols; Drug Synergism; Epithelium; Feeding Behavior; Hyperplasia; Male; Neoplasms, Experimental; Organ Size; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach; Stomach Diseases; Stomach Neoplasms