Heitman D W, Ord V A, Hunter K E, Cameron I L
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Cancer Res. 1989 Oct 15;49(20):5581-5.
The effects of different levels of dietary cellulose on colonic crypt mitotic activity and colon carcinogenesis were studied in 190 male Sprague-Dawley rats. Rats were divided into groups and fed a basal fiber-free diet supplemented with either 0, 5, or 15% pure cellulose (w/w), for periods of 10 weeks (initiation stage) or 32 weeks (promotional stage). Half of the rats in each group were given weekly s.c. injections of 9.5 mg 1,2-dimethylhydrazine (the base) (DMH) for 8 weeks. Some of the rats were killed at 10 weeks while most were killed 22 weeks later. In some groups the dietary cellulose level was changed to a different level at 10 weeks. Food intake and body weight data showed that the rats within each experiment were isocalorically fed. There was a direct correlation between crypt height and the percentage of cellulose in the diet. Addition of 5 or 15% dietary cellulose during the initiation stage of carcinogenesis resulted in a significant increase in crypt height. Increasing dietary cellulose after the initiation stage (0 to 5% and 5 to 15%) or maintaining a high dietary cellulose level throughout both the initiation and promotional stages (15%) resulted in a significant increase in crypt height. A DMH-induced increase in mitotic activity that was observed during the initiation stage was no longer evident after the 22-week promotional stage. The significant DMH-induced increases in proliferative zone height and crypt height that were initially observed during the initiation stage were also observed after the 22-week promotional stage. These data indicate that the initial DMH-induced increases observed in proliferative zone height and crypt height are irreversible. Addition of 5 or 15% cellulose was found to suppress DMH-enhanced mitotic activity in the crypts of the descending colon during the initiation stage of carcinogenesis. This finding was correlated with a significantly lower incidence of adenocarcinomas in rats maintained on 5 or 15% cellulose throughout both the initiation and promotional stages.
在190只雄性斯普拉格 - 道利大鼠中研究了不同水平的膳食纤维素对结肠隐窝有丝分裂活性和结肠癌发生的影响。将大鼠分成几组，喂食不含纤维的基础饮食，并添加0%、5%或15%的纯纤维素（重量/重量），持续10周（启动阶段）或32周（促进阶段）。每组一半的大鼠每周皮下注射9.5毫克1,2 - 二甲基肼（碱基）（DMH），持续8周。一些大鼠在10周时处死，而大多数在22周后处死。在一些组中，膳食纤维素水平在10周时改变为不同水平。食物摄入量和体重数据表明，每个实验中的大鼠均按等热量喂食。隐窝高度与饮食中纤维素的百分比之间存在直接相关性。在致癌作用的启动阶段添加5%或15%的膳食纤维素会导致隐窝高度显著增加。在启动阶段后增加膳食纤维素（从0%增加到5%和从5%增加到15%）或在启动和促进阶段都保持高膳食纤维素水平（15%）会导致隐窝高度显著增加。在启动阶段观察到的DMH诱导的有丝分裂活性增加在22周的促进阶段后不再明显。在22周的促进阶段后也观察到了在启动阶段最初观察到的DMH诱导的增殖区高度和隐窝高度的显著增加。这些数据表明，最初观察到的DMH诱导的增殖区高度和隐窝高度增加是不可逆的。发现在致癌作用的启动阶段添加5%或15%的纤维素可抑制DMH增强的降结肠隐窝中的有丝分裂活性。这一发现与在启动和促进阶段都维持5%或15%纤维素喂养的大鼠中腺癌发生率显著降低相关。
