Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon
Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon
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DOI：
10.1093/carcin/20.4.645
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发表时间：
1999-04-01
期刊：
影响因子：
4.7
通讯作者：
Johnson, IT
中科院分区：
文献类型：
--
作者：
Latham, P;Lund, EK;Johnson, IT
在雄性Wistar大鼠中，在给予1，2-二甲基肼（DMH）后24和48 h，检查了膳食鱼油对结肠隐窝细胞凋亡和增殖的影响，并评估了其对远端结肠异常隐窝病灶（ACF）诱导的影响。大鼠（125-150 g）喂食含玉米油（CO）的高脂肪半合成饲料，给予DMH（30 mg/kg体重）或EDTA/NaCl假注射。然后给动物喂食CO饮食或用鱼油（EPA 18.7%; DHA 8%）代替玉米油的饮食。在24和48 h后处死大鼠亚组（n = 5），并通过形态学标准在来自中段和远端结肠的分离的完整隐窝中定量隐窝细胞凋亡和增殖。鱼油饮食（FO）的消耗与DMH后24小时和48小时结肠隐窝中的凋亡细胞死亡增加（P < 0.001）和增殖抑制（P < 0.05）相关。在第二个实验中，以每周间隔给予动物三次DMH注射或载体假注射。每次注射后48小时，动物喂食CO或FO饮食，但在整个过程中维持CO。18周后测定远端结肠中ACF的数量和隐窝多样性，发现在致癌物给药后48 h内给予FO饮食的动物的ACF显著少于喂食CO饮食的大鼠（P < 0.05）。这些数据表明，饮食中的脂肪酸组成是DMH诱导致癌作用的重要决定因素。结肠隐窝对致癌物和鱼油的增殖和凋亡反应，加上ACF的发生率降低，表明n-3 PUFA可以通过介导增殖和细胞死亡平衡的变化来保护DMH免受致癌作用。
The effect of dietary fish oil on colonic crypt cell apoptosis and proliferation was examined in male Wistar rats, 24 and 48 h after administration of 1,2-dimethylhydrazine (DMH), and its influence on the induction of aberrant crypt foci (ACF) in the distal colon was assessed. Rats (125-150 g) fed a high-fat semi-synthetic diet containing corn oil (CO) were given DMH (30 mg/kg body wt) or a sham injection of EDTA/NaCl. Animals were then fed either the CO diet or a diet in which fish oil (EPA 18.7%; DHA 8%) was substituted for corn oil. Subgroups of rats (n = 5) were killed after 24 and 48 h, and crypt cell apoptosis and proliferation were quantified by morphological criteria in isolated intact crypts from the mid and distal colon. Consumption of the fish oil diet (FO) was associated with increased apoptotic cell death (P < 0.001) and suppression of proliferation (P < 0.05) in colonic crypts both 24 and 48 h after DMH, In a second experiment, animals were given three injections of DMH or sham injections of carrier at weekly intervals. For 48 h after each injection animals were fed either the CO or FO diet, but otherwise maintained on the CO throughout. The number and crypt multiplicity of ACF in the distal colon were determined after 18 weeks, and animals given the FO diet for the 48 h period following carcinogen administration were found to have significantly fewer ACF than rats fed the CO diet (P < 0.05). The data demonstrate that the fatty acid composition of the diet is an important determinant in the induction of carcinogenesis by DMH, The proliferative and apoptotic response of the colonic crypt to carcinogen and fish oil, coupled with the reduced incidence of ACF, suggest n-3 PUFA can protect against the carcinogenic effects of DMH by mediating changes in the balance proliferation and cell death.