Magnuson B A, Bird R P
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
Cancer Lett. 1993 Jan 15;68(1):15-23. doi: 10.1016/0304-3835(93)90214-t.
Recent studies in our laboratory have demonstrated that feeding cholic acid (CHA) to rats treated with a single dose of azoxymethane (AOM) reduces the growth of putative preneoplastic lesions, aberrant crypt foci (ACF), in a dose-dependent manner. This finding was unexpected since CHA has been reported to promote colon cancer in rats receiving multiple treatments of the colon carcinogen, methylnitrosourea (MNU). The main objective of the present investigation was to evaluate the effect of the type of carcinogen and treatment protocol on the induction and growth of ACF in conjunction with CHA treatment. Male Sprague-Dawley rats received 0, 1 or 2 treatments with AOM or MNU and were fed either the AIN-76A or AIN-76A plus 0.2% CHA diet for 4 weeks. The total number and average size of ACF were significantly reduced in CHA-fed animals regardless of the type or number of treatments of carcinogen. The greatest reduction of ACF due to CHA-feeding was seen in the distal colon. The average crypt multiplicity (number of crypts in each ACF) was not altered by diet or carcinogen treatment. Colonic cell proliferation (crypt height and number of mitotic figures) was significantly increased in CHA-fed animals compared to control diet animals. Therefore, feeding CHA for 4 weeks reduced the number and size of ACF in rats induced by 1 or 2 injections of AOM or MNU, despite stimulation of colonic cell proliferation. These findings suggest further investigation is needed to understand the mechanism of promotion by cholic acid and the value of number and growth characteristics of ACF as a biological endpoint in the pathogenesis of colon cancer.
我们实验室最近的研究表明，给单次注射偶氮甲烷（AOM）的大鼠喂食胆酸（CHA），可呈剂量依赖性地减少假定的癌前病变即异常隐窝灶（ACF）的生长。这一发现出人意料，因为据报道，在接受多次结肠致癌物甲基亚硝基脲（MNU）处理的大鼠中，CHA会促进结肠癌。本研究的主要目的是评估致癌物类型和处理方案对与CHA处理相关的ACF诱导和生长的影响。雄性Sprague-Dawley大鼠接受0、1或2次AOM或MNU处理，并喂食AIN-76A或AIN-76A加0.2% CHA的饲料4周。无论致癌物的类型或处理次数如何，喂食CHA的动物中ACF的总数和平均大小均显著降低。喂食CHA导致的ACF减少在结肠远端最为明显。饮食或致癌物处理未改变平均隐窝多倍性（每个ACF中的隐窝数量）。与对照饮食动物相比，喂食CHA的动物结肠细胞增殖（隐窝高度和有丝分裂图数量）显著增加。因此，尽管刺激了结肠细胞增殖，但喂食CHA 4周可减少由1或2次注射AOM或MNU诱导的大鼠中ACF的数量和大小。这些发现表明，需要进一步研究以了解胆酸的促癌机制以及ACF的数量和生长特征作为结肠癌发病机制中生物学终点的价值。
