Kawamori T, El-Bayoumy K, Ji B Y, Rodriguez J G, Rao C V, Reddy B S
Division of Nutritional Carcinogenesis and Division of Cancer Etiology and Prevention, American Health Foundation, Valhalla, NY 10595, USA.
Int J Oncol. 1998 Jul;13(1):29-34. doi: 10.3892/ijo.13.1.29.
Observational, clinical and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. Since toxicity and chemopreventive efficacy of selenium compounds depend to a large extent, on the form of selenium the development of efficacious organoselenium compounds with low toxicity is being pursued in our laboratory. We have assessed the chemopreventive properties of a newly synthesized organoselenium compound, benzyl selenocyanate glutathione conjugate (BSeSG), and of benzyl selenocyanate (BSC), as a positive control, using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 10 or 20 ppm BSeSG (1.7 and 3.4 ppm as Se, respectively), or 10 ppm BSC (4.1 ppm as Se). One week later, all animals except those in vehicle (normal saline)-treated groups were s.c. injected with AOM (15 mg/kg of body weight, once weekly for 2 weeks). All animals were sacrificed 7 weeks after the last AOM injection, and the ACF, levels of prostaglandin E2 (PGE2), cyclooxygenase protein expression (COX-1 and -2), and glutathione S-transferase type mu (GST-mu) were determined in the colon. As expected, dietary administration of BSC suppressed ACF development by about 37%. In rats administered 10 or 20 ppm BSeSG, the frequencies of AOM-induced colonic ACF were significantly decreased compared to those of rats given AOM and control diet by about 41% (P<0.01) and 61% (P<0.001), respectively. Administration of BSeSG inhibited PGE2 production (81-88% inhibition) via COX-2 synthesis in the colonic mucosa (18-60% inhibition). Also, BSeSG increased GST-mu protein activity in colonic mucosa (30-32% increase). These data suggest that a newly synthesized organoselenium compound, BSeSG might be a promising chemopreventive agent against colon carcinogenesis.
观察性、临床和实验研究表明，膳食补充硒可以抑制结肠癌的发展。由于硒化合物的毒性和化学预防效果在很大程度上取决于硒的形式，因此我们实验室正在致力于开发低毒的有效有机硒化合物。我们评估了一种新合成的有机硒化合物苄基硒氰酸谷胱甘肽共轭物（BSeSG）以及作为阳性对照的苄基硒氰酸酯（BSC）的化学预防特性，使用氧化偶氮甲烷（AOM）诱导的结肠异常隐窝灶（ACF）作为疗效指标。将5周龄的雄性F344大鼠喂食对照饮食（改良的AIN-76A）或含有10或20 ppm BSeSG（分别相当于1.7和3.4 ppm的硒）或10 ppm BSC（相当于4.1 ppm的硒）的实验饮食。一周后，除了用赋形剂（生理盐水）处理的组外，所有动物均皮下注射AOM（15 mg/kg体重，每周一次，共2周）。在最后一次注射AOM 7周后处死所有动物，并测定结肠中的ACF、前列腺素E2（PGE2）水平、环氧化酶蛋白表达（COX-1和-2）以及μ型谷胱甘肽S-转移酶（GST-μ）。正如预期的那样，膳食给予BSC可使ACF的发展抑制约37%。在给予10或20 ppm BSeSG的大鼠中，与给予AOM和对照饮食的大鼠相比，AOM诱导的结肠ACF频率分别显著降低了约41%（P<0.01）和61%（P<0.001）。给予BSeSG可通过抑制结肠黏膜中COX-2的合成来抑制PGE2的产生（抑制率为81-88%）（抑制率为18-60%）。此外，BSeSG可增加结肠黏膜中GST-μ蛋白的活性（增加30-32%）。这些数据表明，一种新合成的有机硒化合物BSeSG可能是一种有前途的预防结肠癌发生的化学预防剂。
