Inhibition by dietary oltipraz of experimental intestinal carcinogenesis induced by azoxymethane in male F344 rats.
Inhibition by dietary oltipraz of experimental intestinal carcinogenesis induced by azoxymethane in male F344 rats.
复制标题
膳食奥替普拉对雄性 F344 大鼠中氧化偶氮甲烷诱导的实验性肠道癌的抑制作用。
DOI：
10.1093/carcin/12.6.1051
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发表时间：
1991
期刊：
影响因子：
4.7
通讯作者：
Reddy,BS
中科院分区：
文献类型：
--
作者：
Rao,CV;Tokomo,K;Kelloff,G;Reddy,BS
流行病学研究表明，食用富含二硫代硫肽的十字花科蔬菜与降低人类癌症发病率有关。在雄性F344大鼠中，研究了两种剂量的替代二硫代硫酮ohipraz[5 -（2-吡嗪基）- 4 -甲基- 1,2 -二硫-3-硫酮]对偶氮氧甲烷（AOM）诱导的肠道癌变和血清水平的影响。在雄性F344大鼠中测定了oltipraz的最大耐受剂量（MTD），发现其为500 p.p.m.。在200 p.p.m. （40% MTD）和400 p.p.m. （80% MTD）的饮食水平下，oltipraz作为肠道癌变抑制剂进行了试验。5周龄饲喂改良AIN-76A（对照）饲粮和添加oltipraz的试验饲粮。在7周龄时，除给药动物外，所有动物均给予AOM （15 mg/kg体wt/周，连续2周）s.c注射。拟作载体治疗的动物给予等量生理盐水s.c。52周后处死所有动物，比较各组结肠和小肠肿瘤的发生率和多样性。结果表明，饲喂200和400 p.p.m.的oltipraz能显著抑制大鼠结肠和小肠腺癌的发病率，并能显著抑制大鼠结肠腺瘤和小肠腺癌的多样性。与喂食200 p.m.的oltipraz相比，喂食400 p.m. oltipraz的动物血清中oltipraz的含量有所增加。本研究结果表明，饮食中的奥替praz可抑制肠道癌变。
Epidemiological studies suggest that consumption of cruciferous vegetables rich in dithiolethiones is associated with a reduction in the incidence of cancer in man. The effect of two dose levels of dietary ohipraz [5–(2-pyrazinyl)–4–methyl-1, 2-dithiole-3-thione], a substituted dithiolethione, on azoxymethane (AOM)-induced intestinal carcinogenesis and on serum levels was studied in male F344 rats. The maximum tolerated dose (MTD) of oltipraz was determined in male F344 rats and found to be 500 p.p.m. Oltipraz at levels of 200 p.p.m. (40% MTD) and 400 p.p.m. (80% MTD) diet was tested as inhibitor of intestinal carcinogenesis. At 5 weeks of age, animals were fed the modified AIN-76A (control) diet and experimental diets containing oltipraz. At 7 weeks of age, all animals except the vehicle-treated animals were administered s.c. injection of AOM (15 mg/kg body wt/week for 2 weeks). Animals intended for vehicle treatment were administered s.c. with an equal volume of normal saline. Fifty-two weeks later, all animals were killed and colon and small intestinal tumor incidences and multiplicity were compared among the dietary groups. The results indicate that feeding of 200 and 400 p.p.m. of oltipraz significantly inhibited the incidence of adenocarcinomas in colon and small intestine and multiplicity of colon adenomas and small intestinal adenocarcinomas. Animals fed 400 p.p.m. oltipraz showed increased levels of oltipraz in the serum as compared to those fed 200 p.p.m. oltipraz. The results of this study indicate that dietary oltipraz inhibits intestinal carcinogenesis.