Effect of Feeding Nitrite, Ascorbate, Hemin, and Omeprazole on Excretion of Fecal Total Apparent N-Nitroso Compounds in Mice
Effect of Feeding Nitrite, Ascorbate, Hemin, and Omeprazole on Excretion of Fecal Total Apparent N-Nitroso Compounds in Mice
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DOI：
10.1021/tx8001884
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发表时间：
2008-12-01
影响因子：
4.1
通讯作者：
Gaikwadt, Nilesh W.
中科院分区：
文献类型：
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作者：
Mirvish, Sidney S.;Davis, Michael E.;Gaikwadt, Nilesh W.
研究认为，红色和亚硝酸盐腌制肉诱发结肠癌的主要原因是肉类中含有n -亚硝基化合物。为了探索这一观点，我们之前的研究表明，喂食牛肉和热狗增加了小鼠粪便中总表观n -亚硝基化合物（ANC）的排泄量。在本项目中，成年瑞士小鼠饲喂半纯化饮食和含有添加剂的水7天。第7天收集个体小鼠粪便，干燥，用水提取。提取液与之前一样进行ANC分析。喂食2.0 g亚硝酸钠(NaNO2)/L的饮用水使粪便中ANC水平从5 nmol/g提高到63 nmol/g。在一项剂量反应研究中，粪便ANC水平与亚硝酸盐浓度的平方成正比。32 mg NaNO2/L使粪便ANC水平升高2.3倍（P < 0.05）。在其他结果中，64、125和250 mg血红素/kg饲料中，添加2 g NaNO2/L水，亚硝酸盐的ANC水平分别为2.3、2.2和4.6倍。硝酸钠（12 g/L水）不影响粪便ANC的输出。奥美拉唑（400 mg/kg日粮）和抗坏血酸钠（23 g/kg日粮）分别在饲粮中添加1 g NaNO2/L水时，将粪便中的ANC水平降低了65%和41%，这表明当饲粮中添加亚硝酸盐时，胃中的酸催化反应产生了ANC，并通过肠道进入粪便。测试表明，亚硝基硫醇约占粪便和热狗ANC的20%。到目前为止，观察到的NaNO2效应与提出的假设不一致。母鸡锡的增强可能有助于解释为什么红肉是结肠癌的原因。
It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current project, adult Swiss mice were fed a semipurified diet and water containing additives for 7 days. Feces from individual mice was collected on day 7, dried, and extracted with water. Extracts were analyzed for ANC as before. Feeding 2.0 g sodium nitrite (NaNO2)/L drinking water raised fecal ANC levels from 5 to 63 nmol/g feces. In a dose-response study, fecal ANC levels were proportional to the nitrite concentration squared. Even 32 mg NaNO2/L raised fecal ANC levels 2.3-fold (P < 0.05). In other results, 64, 125, and 250 mg hemin/kg diet, fed with 2 g NaNO2/L water, showed 2.3, 2.2, and 4.6 times the ANC level for nitrite alone. Sodium nitrate (12 g/L water) did not affect fecal ANC output. Omeprazole (400 mg/kg diet) and sodium ascorbate (23 g/kg diet), when fed with 1 g NaNO2/L water, lowered fecal ANC levels by 65 and 41%, indicating that, when nitrite was fed, acid-catalyzed reactions in the stomach produced ANC, which passed down the gut to the feces. Tests indicated that nitrosothiols constituted about 20% of fecal and hot dog ANC. The observed effect of NaNO2 is thus far not consistent with the proposed hypothesis. The enhancement by hen-tin may help explain why red meat is a cause of colon cancer.