Prevention by retinoids of azoxymethane-induced tumors and aberrant crypt foci and their modulation of cell proliferation in the colon of rats.
Prevention by retinoids of azoxymethane-induced tumors and aberrant crypt foci and their modulation of cell proliferation in the colon of rats.
复制标题
通过类维生素A预防氧化偶氮甲烷诱导的肿瘤和异常隐窝病灶及其对大鼠结肠细胞增殖的调节。
DOI：
10.1093/carcin/18.11.2119
复制
发表时间：
1997
期刊：
影响因子：
4.7
通讯作者：
Pereira,MA
中科院分区：
文献类型：
--
作者：
Zheng,Y;Kramer,PM;Olson,G;Lubet,RA;Steele,VE;Kelloff,GJ;Pereira,MA
Retinoids are proposed chemopreventive agents that inhibit cell proliferation and induce differentiation. Their ability to prevent azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors and to modulate cell proliferation was investigated in the colon of male F344 rats. Thirteen retinoids were evaluated for prevention of ACF and two of them, 9-cis-retinoic acid (RA) and 4-(hydroxyphenyl)retinamide (4-HPR), were also evaluated for prevention of colon cancer. The retinoids were administered continuously in the diet starting 1 week prior to the first of two weekly 15 mg/kg i.p. injections of AOM and for a total of either 5 or 36 weeks in order to evaluate their effect on colonic ACF and tumors. At a concentration of 1 mmol/kg diet, 2-(carboxyphenyl)retinamide caused the greatest reduction (57.7%) in the yield of ACF. 9-cis-RA was toxic at 1 mmol/kg so that it was evaluated at 0.1 mmol/kg, resulting in a 41.6% reduction in ACF. The ability of the retinoids to reduce the proliferating cell nuclear antigen (PCNA) labeling index in ACF and in non-involved crypts correlated with their ability to prevent ACF. Both 9-cis-RA (0.1 and 0.2 mmol/kg diet) and 4-HPR (1 and 2 mmol/kg diet) were highly effective in decreasing the yield of AOM-induced colon tumors. In summary, retinoids were demonstrated to reduce cell proliferation and to prevent ACF and tumors in the colon, suggesting promise as preventive agents for colon cancer.
