Takahashi M, Totsuka Y, Masuda M, Fukuda K, Oguri A, Yazawa K, Sugimura T, Wakabayashi K
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Carcinogenesis. 1997 Oct;18(10):1937-41. doi: 10.1093/carcin/18.10.1937.
Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of aberrant crypt foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic aberrant crypt foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1-5 and 8-12) with or without intragastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced aberrant crypt foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38% respectively of the values obtained when PhIP alone was used. The mean number of aberrant crypts per focus was also decreased by DHA treatment. At week 4 the PhIP-DNA adduct levels in the colon of rats from the PhIP+DHA group were approximately two thirds of the PhIP group value. The results thus suggest that DHA exerts a preventive effect on PhIP-induced colon carcinogenesis.
二十二碳六烯酸（DHA）是鱼油的主要成分，可抑制由1,2 - 二甲基肼和偶氮甲烷诱导的异常隐窝灶的形成和生长。在本研究中，我们检测了经胃灌胃给予DHA对用杂环胺2 - 氨基 - 1 - 甲基 - 6 - 苯基咪唑[4,5 - b]吡啶（PhIP）处理的大鼠结肠异常隐窝灶产量的影响，PhIP可在雄性F344大鼠中诱发结肠癌，被认为是一种可能的人类结肠致癌物。雄性F344大鼠给予标准饮食（AIN - 76A），在每次致癌物处理前4小时，给予10剂PhIP（75mg/kg体重，经胃插管，在第1 - 5天和第8 - 12天），同时有或没有经胃给予1ml DHA，随后进一步给予DHA剂量。给予DHA 4周和12周后，每只结肠中PhIP诱导的异常隐窝灶数量分别显著降低至单独使用PhIP时所得值的47%和38%。DHA处理还使每个病灶中异常隐窝的平均数量减少。在第4周时，PhIP + DHA组大鼠结肠中的PhIP - DNA加合物水平约为PhIP组值的三分之二。因此，结果表明DHA对PhIP诱导的结肠癌发生具有预防作用。
