Fish oil blocks azoxymethane-induced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation
Fish oil blocks azoxymethane-induced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation
复制标题
DOI：
10.1093/jn/128.3.491
复制
发表时间：
1998-03-01
影响因子：
4.2
通讯作者：
Lupton, JR
中科院分区：
文献类型：
--
作者：
Chang, WCL;Chapkin, RS;Lupton, JR
本研究的目的是确定鱼油对结肠癌发生的保护作用是否是由于增殖减少，分化增加和/或凋亡增加。雄性Sprague道利大鼠（n = 260）喂食两种油（玉米或鱼）和两种纤维（果胶或纤维素）之一，加上或减去致癌物氧化偶氮甲烷（AOM）。在第18周（n = 80）或第36周（n = 180）处死大鼠进行细胞动力学测量。在体内细胞增殖的溴脱氧尿苷掺入DNA，分化的结合双花扁豆凝集素和凋亡的地高辛标记的基因组DNA的免疫过氧化物酶检测。与玉米油相比，鱼油导致腺癌发生率较低（56.1 vs. 70.3%）。在近端或远端结肠中，脂肪或纤维对增殖细胞/隐窝柱的数量没有影响。相比之下，鱼油导致更大程度的分化相比，玉米油在两个结肠网站。此外，与玉米油相比，鱼油导致近端和远端结肠中凋亡细胞/隐窝柱的数量更高。AOM处理增加了近端和远端结肠中增殖细胞/隐窝柱与凋亡细胞/隐窝柱的比率。然而，与玉米油相比，鱼油导致结肠两个部位的比例均较低。这些结果表明，细胞凋亡和分化的增加，而不是增殖的减少，占鱼油对实验诱导的结肠肿瘤发生的保护作用。
The purpose of this study was to determine whether the protective effect of fish oil against colon carcinogenesis is due to decreased proliferation, increased differentiation and/or increased apoptosis. Male Sprague Dawley rats (n = 260) were fed one of two oils (corn or fish) and two fibers (pectin or cellulose), plus or minus the carcinogen azoxymethane (AOM). Rats were killed at wk 18 (n = 80) or 36 (n = 180) for cytokinetic measurements. In vivo cell proliferation was measured by incorporation of bromodeoxyuridine into DNA, differentiation by binding of Dolichos biflorus agglutinin and apoptosis by immunoperoxidase detection of digoxigenin labeled genomic DNA. Fish oil resulted in a lower adenocarcinoma incidence (56.1 vs. 70.3%) compared with corn oil. There was no effect of fat or fiber on number of proliferative cells/crypt column in either the proximal or distal colon. In contrast, fish oil resulted in a greater degree of differentiation compared with corn oil in both colonic sites. In addition, fish oil resulted in a higher number of apoptotic cells/crypt column in both the proximal and distal colon as compared with corn oil. AOM treatment increased the ratio of proliferative cells/crypt column to apoptotic cells/crypt column in both the proximal and distal colon compared with saline controls. Fish oil, however, resulted in a lower ratio in both sites in the colon as compared with corn oil. These results suggest that an increase in apoptosis and differentiation, rather than a decrease in proliferation, accounts for the protective effect of fish oil against experimentally induced colon tumorigenesis.