Inhibitory effect of dietary monoglucosylceramide 1-O-β-glucosyl-N-2′-hydroxyarachidoyl-4,8-sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2-dimethylhydrazine in F344 rats
Inhibitory effect of dietary monoglucosylceramide 1-O-β-glucosyl-N-2′-hydroxyarachidoyl-4,8-sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2-dimethylhydrazine in F344 rats
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DOI：
10.1111/j.1349-7006.2005.00127.x
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发表时间：
2005-12-01
期刊：
影响因子：
5.7
通讯作者：
Yoshimi, N
中科院分区：
文献类型：
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作者：
Inamine, M;Suzui, M;Yoshimi, N
鞘磷脂具有广泛的生物活性，包括细胞生长、分化和凋亡。然而，这些化合物发挥抗癌或防癌作用的确切机制尚不清楚。在本研究中，我们评价了强化饮食单糖神经酰胺1-O-beta-glucosyl-N-2‘-hydroxyarachidoyl-4，8-sphingadienine(G(1)CM)对1，2-二甲基肼诱导的F344大鼠在发育期形成的异常隐窝和β-连环蛋白蓄积隐窝的预防作用。我们还检测了G、CM是否影响这些病变的细胞增殖和凋亡。从米糠中分离得到了纯的G1CM。将42只大鼠随机分为5个实验组。第1~3组大鼠皮下注射DMH(40 mg/kg体重)，每周1次，连续2周。在第一次注射DMH前一周，第2组和第3组大鼠分别喂以每分钟200和1000的饲料。GCM组，分别治疗5周。第4组大鼠喂饲含1000p.p.m的饲料。G1CM。第5组大鼠仅给予基础饲料喂养，作为未处理的对照组。实验在开始5周后终止。与DMH单独处理组1相比，两个剂量的G1CM(组2和组3)显著抑制了ACF和BCAC的诱导(P<；0.001)。2、3组ACF和BCAC上皮细胞增殖细胞核抗原标记指数均低于1组(P<0.0001)。这些结果表明，饮食中的G1CM在目前的短期结肠癌发生生物检测中可能具有化学预防作用，表明较长时间的暴露可能会抑制肿瘤的发展。
Sphingolipids display a wide spectrum of biological activities, including cell growth, differentiation and apoptosis. However, precise mechanisms by which these compounds exert anticancer or cancer-preventive effects are not known. In the present study, we evaluated the preventive efficacy of enriched dietary monoglucosylceramid 1-O-beta-glucosyl-N-2'-hydroxyarachidoyl-4,8-sphingadienine (G(1)CM) on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and beta-catenin-accumulated crypt (BCAC) formation in F344 rats during initiation stage. We also examined whether G,CM affects cell proliferation and apoptosis in these lesions. Pure G1CM was isolated from rice bran. Forty-two rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of DMH (40 mg/kg body weight) once a week for 2 weeks. One week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 200 and 1000 p.p.m. GCM, respectively, for 5 weeks. Rats in group 4 were fed a diet containing 1000 p.p.m. G1CM. Rats in group 5 were given the basal diet alone and served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary G1CM at both doses (groups 2 and 3) significantly inhibited the induction of ACF and BCAC (P < 0.001) when compared to group 1 treated with DMH alone. In groups 2 and 3, the proliferating cell nuclear antigen labeling indices of epithelial cells in ACF and BCAC were also lower than in group 1 (P < 0.0001 for ACF, P < 0.05 for BCAC). These results, that dietary G1CM has possible chemopreventive effects in the present short-term colon carcinogenesis bioassays, suggest that longer exposure may cause suppression of tumor development.