Baines A T, Holubec H, Basye J L, Thorne P, Bhattacharyya A K, Spallholz J, Shriver B, Cui H, Roe D, Clark L C, Earnest D L, Nelson M A
Pharmacology/Toxicology Department, The University of Arizona, Tucson, AZ, USA.
Cancer Lett. 2000 Nov 28;160(2):193-8. doi: 10.1016/s0304-3835(00)00585-1.
We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.
我们评估了膳食补充硒代蛋氨酸对结肠多胺水平的影响,以及补充L-硒代蛋氨酸对大鼠结肠中偶氮甲烷(AOM)致癌活性的调节能力。四周龄雄性F344大鼠每周一次接受15mg/kg体重的AOM处理,共2周。将浓度为1或2ppm的膳食硒代蛋氨酸添加到AIN-76A啮齿动物饲料中,给予经AOM处理的动物,持续16周。在16周的治疗过程后,对结肠癌前病变异常隐窝灶(ACF)进行了研究。饮食中给予2ppm的硒代蛋氨酸可显著减少异常隐窝灶的数量。ACF的多发性(即每个病灶中异常隐窝的数量)和微腺瘤的百分比也受到硒代蛋氨酸的剂量依赖性影响。然而,对照组和处理组之间结肠组织多胺水平的评估显示无显著差异。这些结果表明,硒代蛋氨酸可通过不依赖多胺的机制调节AOM诱导的癌前病变的发展。