Combined inhibitors of carcinogenesis: effect on azoxymethane-induced intestinal cancer in rats.
Combined inhibitors of carcinogenesis: effect on azoxymethane-induced intestinal cancer in rats.
复制标题
致癌作用的联合抑制剂：对氧化偶氮甲烷诱导的大鼠肠癌的作用。
DOI：
--
复制
发表时间：
1982
期刊：
影响因子：
--
通讯作者：
M. Alousi
中科院分区：
文献类型：
--
作者：
N. Nigro;A. Bull;P. Wilson;B. K. Soullier;M. Alousi
远交雄性Sprague-Dawley CD大鼠喂食完全半合成饮食，并在其饮用水中补充低剂量（2 ppm）硒（以H2SeO 3形式）或50 mg 13-顺式-视黄酸（13-cis-RA）和2 g β-谷甾醇/kg饮食（单独、两种组合或所有三种组合）。用8 mg氧化偶氮甲烷（AOM）/kg体重皮下注射8周诱导肠肿瘤，26周后通过肿瘤计数确定肿瘤形成的抑制。每个饮食组的非致癌物对照组接受8次无菌水注射。在2组动物中肿瘤抑制具有统计学显著性：饮食对照动物的肿瘤频率为5.07个肿瘤/大鼠，接受硒加13-顺式-RA补充的大鼠的肿瘤频率为3.77个肿瘤/大鼠，并且给予所有三种抑制剂的组合的那些具有2.75个肿瘤/大鼠。对3个AOM组（饮食对照组、β-谷甾醇加13-顺式-RA补充组和接受所有三种添加剂的组）在补充4个月后的粪便类固醇分析表明，在饮食中添加β-谷甾醇对酸性或中性类固醇没有影响，无论观察到的肿瘤频率差异如何。这些结果表明，亚药理学剂量的抑制剂，特别是那些通过不同机制抑制该过程的抑制剂，虽然单独无效，但当联合使用时，可能会显著抑制肿瘤发生。
Outbred male Sprague-Dawley CD rats were fed a complete semisynthetic diet and were given supplemental low doses (2 ppm) of selenium as H2SeO3 in their drinking water or 50 mg 13-cis-retinoic acid (13-cis-RA) and 2 g beta-sitosterol/kg diet either singly, in combinations of two, or in combinations of all three. Intestinal tumors were induced with eight weekly sc injections of 8 mg azoxymethane (AOM)/kg body weight, and inhibition of tumor formation was determined by tumor counts after 26 weeks. Noncarcinogen controls for each dietary group received eight injections of sterile water. Tumor inhibition was statistically significant in 2 groups of animals: Dietary control animals had a tumor frequency of 5.07 tumors/rat, rats receiving selenium- plus 13-cis-RA supplementation had a tumor frequency of 3.77, and those being given the combination of all three inhibitors had 2.75 tumors/rat. Analysis of fecal steroids from 3 AOM groups (dietary controls, the beta-sitosterol plus 13-cis-RA-supplemented group, and the group receiving all three additives) after 4 months of supplementation showed that the addition of beta-sitosterol to the diet had no effect on acidic or neutral steroids, regardless of the observed difference in tumor frequency. These results suggest that subpharmacologic doses of inhibitors, particularly those that inhibit the process by different mechanisms, while ineffective alone, may provide significant inhibition of tumorigenesis when used in combination.