Kawabe M, Takaba K, Yoshida Y, Hirose M
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1994 Jan;85(1):17-25. doi: 10.1111/j.1349-7006.1994.tb02881.x.
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.
在F344大鼠中研究了亚硝酸钠（NaNO2）与酚类化合物联合处理对N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱发胃癌的影响。在第一个实验中，将15 - 20只雄性大鼠分为几组，每组给予150 mg/kg体重的MNNG灌胃剂量，1周后开始，分别单独给予2.0%丁基羟基茴香醚、0.8%儿茶酚、2.0% 3-甲氧基儿茶酚或基础饲料，或者与饮用水中0.2%的NaNO2联合给予，直至在第52周处死。所有三种抗氧化剂均显著增强了前胃致癌作用，额外的NaNO2处理没有任何影响。然而，在没有MNNG预处理的情况下，NaNO2联合处理显著增加了儿茶酚和3-甲氧基儿茶酚组的前胃增生程度。在第二个实验中，研究了各种酚类化合物和NaNO2对消化道上段细胞增殖的联合作用。将5只大鼠分为一组，分别单独给予24种酚类化合物中的一种或基础饲料，或者与0.3%的NaNO2联合给予4周，然后处死。叔丁基对苯二酚（TBHQ）、儿茶酚、没食子酸、1,2,4-苯三酚、dl-3-(3,4-二羟基苯基)-丙氨酸和对苯二酚与NaNO2联合处理对前胃黏膜厚度有特别强的增强作用。在腺胃中，11种情况有类似的增强作用，在食管中，苯酚、TBHQ和没食子酸有类似作用。这些结果表明，NaNO2可以增强各种酚类化合物诱导的胃上皮细胞增殖。
