THE EFFECT OF CHENODEOXYCHOLIC ACID ON THE DEVELOPMENT OF ABERRANT CRYPT FOCI IN THE RAT COLON
THE EFFECT OF CHENODEOXYCHOLIC ACID ON THE DEVELOPMENT OF ABERRANT CRYPT FOCI IN THE RAT COLON
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DOI：
10.1016/0304-3835(94)90384-0
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发表时间：
1994-01-30
期刊：
影响因子：
9.7
通讯作者：
BIRD, RP
中科院分区：
文献类型：
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作者：
SUTHERLAND, LAM;BIRD, RP
据报道，胆汁酸可增强实验诱导的结肠肿瘤发生。以前我们曾报道过胆酸，一种已知的肿瘤促进剂，实际上减少了异常隐窝病灶（ACF）的数量，即所谓的癌前病变（B.A. Magnuson和R.P. Bird，Cancer Lett.，68（1993），15-23）。这一观察结果是出乎意料的，并促使我们探索其他胆汁酸对ACF发展的影响。本研究的主要目的是评估饲喂不同剂量的鹅去氧胆酸（CDC）对ACF的诱导和生长以及对结肠上皮增殖指数的影响。Sprague-Dawley雄性大鼠注射氧化偶氮甲烷（+AOM，20 mg/kg）或生理盐水（-AOM）。一周后，他们被随机分配到五个组，并喂食含有不同水平（0.0，0.025，0.05，0.1和0.2%重量）的CDC的饮食2周。饲养期结束后，定量ACF的数量和隐窝多样性，并测定三种不同的增殖指数，包括有丝分裂指数，BUDR标记指数（S期细胞百分比）和增殖细胞核抗原标记指数（循环细胞百分比）。所有剂量的CDC均增加了ACF的数量，在0.1%CDC水平下具有最大效果。与+AOM对照组相比，CDC喂养+AOM组的隐窝高度显著增加。与0% CDC-AOM组相比，仅0. 025% CDC-AOM组结肠隐窝的有丝分裂指数较高（P小于或等于0. 05）（5. 97 +/-0. 63 vs. 3. 92 +/-0. 79）。BUDR标记指数不受CDC喂养的影响（P>或等于0.05）。PCNA标记指数在CDC喂养组中持续增加。在-AOM组中，0.05%CDC组具有最大值，其与对照值显著不同（分别为19.21 +/- 1.92 vs. 10.93 +/- 0.56）。在+AOM组中，PCNA标记指数随着CDC水平的增加而增加。结论：CDC刺激ACF的发展，并改变结肠隐窝发生肿瘤性变化的细胞周期相关事件。
Bile acids are reported to enhance experimentally-induced colonic tumorigenesis. Previously we have reported that cholic acid, a known tumor promoter, actually reduced the number of aberrant crypt foci (ACF), purported preneoplastic lesions (B.A. Magnuson and R.P. Bird, Cancer Lett., 68 (1993), 15-23). This observation was unexpected and has prompted us to explore the effect of other bile acids on the development of ACF. The primary objective of this investigation was to evaluate the effect of feeding varying dosages of chenodeoxycholic acid (CDC) on the induction and growth of ACF and on the proliferative indices of the colonic epithelium. Sprague-Dawley male rats were injected with azoxymethane (+AOM, 20 mg/kg) or saline (-AOM). One week later they were randomly allocated to five groups and were fed diets containing CDC at varying levels (0.0, 0.025, 0.05, 0.1 and 0.2% by weight) for 2 weeks. After completion of the feeding period the number and crypt multiplicity of ACF were quantified, and three different proliferative indices, including mitotic index, BUDR labelling index (percentage S-phase cells) and proliferating cell nuclear antigen labelling index (percentage cycling cells) were determined. CDC at all dosages increased the number of ACF having the maximum effect at the 0.1% CDC level. A significant dose-related increase in crypt height was noted in CDC-fed +AOM groups when compared with the +AOM control groups. The mitotic indices of colonic crypts were higher (P less than or equal to 0.05) only in the 0.025% CDC -AOM group when compared with the 0% CDC -AOM group (5.97 +/- 0.63 vs. 3.92 +/- 0.79). The BUDR labelling indices were not altered by CDC feeding (P greater than or equal to 0.05). PCNA labelling indices increased consistently among the CDC-fed groups. Among the -AOM group the 0.05% CDC group had the maximum value, which was significantly different from the control value(19.21 +/- 1.92 vs. 10.93 +/- 0.56, respectively). Among the +AOM groups the PCNA labelling indices increased with increasing levels of CDC. It was concluded that CDC stimulated the development of ACF and altered cell cycle associated events in colonic crypts undergoing neoplastic changes.