Effect of dietary deoxycholic acid and cholesterol on fecal steroid concentration and its impact on the colonic crypt cell proliferation in azoxymethane-treated rats
Effect of dietary deoxycholic acid and cholesterol on fecal steroid concentration and its impact on the colonic crypt cell proliferation in azoxymethane-treated rats
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DOI：
10.1016/s0304-3835(97)00452-7
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发表时间：
1998-02-13
期刊：
影响因子：
9.7
通讯作者：
Morotomi, M
中科院分区：
文献类型：
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作者：
Hori, T;Matsumoto, K;Morotomi, M
为了阐明粪便类固醇在结肠上皮细胞恶性肿瘤形成中的作用，我们研究了饲料中脱氧胆酸(DCA)和胆固醇(CHL)对粪便类固醇浓度的影响及其对结肠隐窝细胞增殖的影响。20只5周龄雄性Fischer 344大鼠分为对照组和添加0.15%DCA和1%CHL(类固醇饲料)的对照组。在注射了偶氮甲烷(AOM)(一种已知的胃肠道致癌物质)或生理盐水的大鼠中，比较了这两种饮食的效果。在2×2析因设计中，喂饲这些饲料的大鼠每周两次皮下注射AOM(15毫克/公斤体重)。或在6周龄和7周龄时注射生理盐水。9周龄时取粪样进行胆汁酸、胆红素及其肠道菌群细菌代谢物分析。在10周龄时，动物被处死，结肠增殖被评估为每个隐窝累积的长春新碱有丝分裂图形。与对照组相比，服用类固醇饮食的大鼠的粪便胆汁酸(5倍，P<；0.001)和中性类固醇(10倍，P<；0.01)水平显著升高。AOM治疗似乎不影响这些水平。然而，与两种饮食中注射生理盐水的对照组相比，注射青蒿素的大鼠的结肠细胞增殖率显著增加(P<；0.001)。此外，喂食类固醇饮食的大鼠的细胞增殖率明显高于喂食对照饮食的老鼠(P<；0.001)。AOM处理和激素饮食对细胞增殖的影响是相加的。我们的结果表明，结肠腔中高浓度的中性类固醇和酸性类固醇可以促进致癌物诱导的细胞增殖，因此可能在结肠癌的病因中发挥关键作用。(C)1998年爱思唯尔爱尔兰科学有限公司。
To elucidate the role of fecal steroids in the malignant tumor formation of colonic epithelial cells, we examined the effects of dietary deoxycholic acid (DCA) and cholesterol (CHL) on fecal steroid concentrations and their impact on colonic crypt cell proliferation. Twenty 5-week-old male Fischer 344 rats were provided with either a control semisynthetic diet or the same diet supplemented with 0.15% DCA and 1% CHL (steroid diet) over a 5-week period. The effects of these two diets were compared among rats that were either injected with azoxymethane (AOM), a known gastrointestinal carcinogen, or saline. In a 2 x 2 factorial design, rats fed each of these diets were given two weekly subcutaneous injections of either AOM (15 mg/kg b.w.) or saline at 6 and 7 weeks of age. At 9 weeks of age, fecal samples were obtained for analysis of bile acids, CHL and its bacterial metabolites of intestinal microflora. At 10 weeks of age, animals were sacrificed and colonic proliferation was assessed as vincristine-accumulated mitotic figures per crypt. Rats fed the steroid diet had significantly elevated fecal bile acid (5x, P < 0.001) and neutral steroid (10x, P < 0.01) levels when compared to those fed the control diet. AOM treatment did not appear to influence these levels. However, rats injected with AOM had a significant increase (P < 0.001) in their rate of colonic cell proliferation as compared to saline-injected control animals on both diets. Furthermore, rats fed the steroid diet had a significantly higher (P < 0.001) cell proliferation rate than animals fed the control diet. The effects of AOM treatment and the steroid diet on cell proliferation were additive. Our results demonstrate that high concentrations of neutral and acid steroids in the colonic lumen can enhance carcinogen-induced elevated cell proliferation and thus may play a key role in the etiology of colon cancer. (C) 1998 Elsevier Science Ireland Ltd.