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在雄性F344大鼠中,通过饮食给予甲硫氨酸甲基磺酸酯对氧化偶氮甲烷诱导的结肠癌发生进行化学预防。

Chemoprevention of azoxymethane-induced colon carcinogenesis by dietary feeding of S-methyl methane thiosulfonate in male F344 rats.

作者信息

Kawamori T, Tanaka T, Ohnishi M, Hirose Y, Nakamura Y, Satoh K, Hara A, Mori H

机构信息

First Department of Pathology, Gifu University School of Medicine, Japan.

出版信息

Cancer Res. 1995 Sep 15;55(18):4053-8.

PMID:7664279
Abstract

Modifying effects of dietary exposure of S-methyl methane thiosulfonate (MMTS) isolated from cauliflower Brassica oleracea L. var. botrytis on rat colon carcinogenesis induced by azoxymethane (AOM) and on the expression of cell proliferation biomarkers were investigated in two experiments. In experiment 1, male F344 rats were given three s.c. injections of AOM (15 mg/kg body weight) and fed 100 ppm MMTS for 5 weeks, starting 1 week before the first dose of AOM. The frequency of colonic aberrant crypt foci was determined at 5 weeks after the start. Feeding of 100 ppm MMTS for 5 weeks significantly decreased the number of aberrant crypt foci/colon. Colonic mucosal ornithine decarboxylase activity and the number of silver-stained nucleolar organizer regions per nucleus in colonic epithelium were significantly decreased by MMTS treatment compared with those of AOM alone. In experiment 2, effects of dietary feeding of MMTS at two doses (20 and 100 ppm) during the postinitiation phase on intestinal tumorigenesis initiated with AOM were investigated by using a long-term experiments in male F344 rats. Incidence of intestinal neoplasms of rats fed MMTS-containing diets after AOM exposure were reduced in a dose-dependent manner. Feeding of MMTS during the postinitiation phase decreased the number of aberrant crypt foci/colon, colonic ornithine decarboxylase activity, 5-bromodeoxyuridine-labeling index in colonic epithelium, and polyamine level in blood compared with those of AOM alone. These results suggest that MMTS might be a possible chemopreventive agent for intestinal neoplasia.

摘要

在两项实验中,研究了从花椰菜(甘蓝变种)中分离出的S-甲基甲硫代磺酸盐(MMTS)的膳食暴露对由氧化偶氮甲烷(AOM)诱导的大鼠结肠癌发生的修饰作用以及对细胞增殖生物标志物表达的影响。在实验1中,雄性F344大鼠接受三次皮下注射AOM(15毫克/千克体重),并在第一剂AOM前1周开始喂食100 ppm的MMTS,持续5周。在开始后5周测定结肠异常隐窝病灶的频率。喂食100 ppm的MMTS持续5周可显著减少异常隐窝病灶/结肠的数量。与单独使用AOM相比,MMTS处理显著降低了结肠黏膜鸟氨酸脱羧酶活性以及结肠上皮细胞核中银染核仁组织区的数量。在实验2中,通过对雄性F344大鼠进行长期实验,研究了在启动后阶段以两种剂量(20和100 ppm)膳食喂食MMTS对由AOM引发的肠道肿瘤发生的影响。AOM暴露后喂食含MMTS饮食的大鼠肠道肿瘤发生率呈剂量依赖性降低。与单独使用AOM相比,在启动后阶段喂食MMTS可减少异常隐窝病灶/结肠的数量、结肠鸟氨酸脱羧酶活性、结肠上皮细胞中的5-溴脱氧尿苷标记指数以及血液中的多胺水平。这些结果表明,MMTS可能是一种潜在的肠道肿瘤化学预防剂。

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