Bird R P
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
Cancer Lett. 1995 Jan 27;88(2):201-9. doi: 10.1016/0304-3835(94)03618-s.
We previously reported that the colons of animals injected with azoxymethane (AOM) and fed a diet containing cholic acid (CHA) had lower numbers of aberrant crypt foci (ACF) than those in animals fed a control diet. To follow up on this observation, a series of studies was conducted to determine whether CHA affects the development of ACF in a dose- and time-dependent manner, and the possible mechanism(s) involved. Sprague Dawley male rats were injected with AOM (20 mg/kg s.c.), and one week later randomly allocated to groups fed diets containing 0, 0.05, 0.1 or 0.2% CHA by weight, for 4 weeks. Their colons were scored for the number size and location of ACF, number of crypts per ACF, and mitotic activity. It was observed that the number and size of ACF decreased with increasing levels of CHA. Mitotic activity was higher (P < 0.05) in the 0.2% CHA diet (CHA-diet) group compared to the 0% CHA group. To determine if timing of intervention with the CHA-diet was critical, rats were allocated to the CHA-diet before or after AOM injection. The ACF-reducing effect of 0.2% CHA diet was evident (P < or = 0.05) only after AOM injection. Intervention with the CHA-diet 4 weeks after AOM injection demonstrated that the diet eliminated and/or remodelled a large proportion (50%) of ACF which had developed within 4 weeks and inhibited the growth of those ACF that persisted. This effect was also associated with higher (P < or = 0.05) mitotic activity in the colon. Discontinuing the treatment of rats with the CHA-diet resulted in a rapid increase in the number of ACF in their colons, establishing that the growth inhibitory effect of the CHA-diet on ACF was reversible. In conclusion, it was demonstrated that the CHA-diet modulated the number of ACF by inhibiting their development and growth and by eliminating or remodelling a selected population of ACF.
我们之前报道过，注射了偶氮甲烷（AOM）并喂食含胆酸（CHA）饮食的动物结肠中，异常隐窝灶（ACF）的数量比喂食对照饮食的动物少。为了跟进这一观察结果，我们进行了一系列研究，以确定CHA是否以剂量和时间依赖性方式影响ACF的发展以及其中可能涉及的机制。将斯普拉格-道利雄性大鼠注射AOM（20mg/kg，皮下注射），一周后随机分为几组，分别喂食含0、0.05、0.1或0.2%（重量）CHA的饮食，持续4周。对它们的结肠进行ACF数量、大小和位置、每个ACF的隐窝数量以及有丝分裂活性的评分。观察到随着CHA水平的增加，ACF的数量和大小减少。与0%CHA组相比，0.2%CHA饮食（CHA饮食）组的有丝分裂活性更高（P<0.05）。为了确定CHA饮食干预的时间是否至关重要，在AOM注射之前或之后将大鼠分配到CHA饮食组。仅在AOM注射后，0.2%CHA饮食降低ACF的效果才明显（P≤0.05）。在AOM注射4周后进行CHA饮食干预表明，该饮食消除和/或重塑了在4周内形成的大部分（50%）ACF，并抑制了那些持续存在的ACF生长。这种效果还与结肠中更高（P≤0.05）的有丝分裂活性相关。停止用CHA饮食对大鼠的治疗导致其结肠中ACF数量迅速增加，这表明CHA饮食对ACF的生长抑制作用是可逆的。总之，研究表明CHA饮食通过抑制ACF的发展和生长以及消除或重塑特定群体的ACF来调节ACF的数量。
