Programmed cell death, proliferating cell nuclear antigen and p53 expression in mouse colon mucosa during diet-induced tumorigenesis.
Programmed cell death, proliferating cell nuclear antigen and p53 expression in mouse colon mucosa during diet-induced tumorigenesis.
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DOI：
10.1155/2000/640396
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Lipkin M
中科院分区：
文献类型：
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作者：
Risio M;Sarotto I;Rossini FP;Newmark H;Yang K;Lipkin M
西式饮食（WD）触发并维持小鼠结肠肿瘤发生的早期阶段，并在整个生命周期中持续导致发育不良隐窝的发展。为了评价细胞增殖和程序性细胞死亡（PCD）在WD诱导的肿瘤发生中的作用，在两种WD长时间喂养的小鼠结肠粘膜中进行增殖核抗原（PCNA）、DNA断裂的原位末端标记（TUNEL）和p53蛋白的免疫组织化学检测。仅在营养研究开始时，WD给药动物的结肠隐窝PCNA标记指数显著高于对照动物，差距通过衰老期间结肠粘膜中自发发生的细胞增殖增加迅速弥合。在WD组中还观察到隐窝基部的短暂早期稳态PCD激活。在整个研究中，在隐窝的上三分之一或表面上皮中未观察到PCD的变化，表明该结肠隐窝段中的PCD产生恒定的细胞损失通量，不受稳态波动的影响。一个主要发现是对照组和给药组动物中隐窝基底PCD的不可逆、进行性、年龄相关性下降，发生在啮齿动物寿命的后半期。p53蛋白未被化学检测到，表明野生型或突变形式的蛋白质的过表达均不参与上述变化。
Western‐style diets (WDs) trigger and sustain the early phases of tumorigenesis in mouse colon, and when continued throughout the life span lead to the development of dysplastic crypts. In order to evaluate the roles both of cell proliferation and programmed cell death (PCD) in WD‐induced tumorigenesis, immunohistochemical detection of proliferating nuclear antigen (PCNA), in situ end labeling (TUNEL) of DNA breaks, and p53 protein were carried out in mouse colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of colonic crypts was significantly higher in WD‐treated animals than in controls only at the beginning of the nutritional study, the gap rapidly bridged by increased cell proliferation spontaneously occurring in the colonic mucosa during aging. A transient early homeostatic activation of PCD at the base of the crypt also was observed in WD groups. No changes in PCD were seen in the upper third of the crypt or in surface epithelium throughout the study, indicating that PCD in that colonic crypt segment produces a constant flux of cell loss, uninfluenced by homeostatic fluctuations. A major finding was an irreversible, progressive, age‐related decline of PCD at the crypt base in both control and treated animals that occurred during the second half of the rodents life span. p53 protein was not immunohistochemically detected, suggesting that neither overexpression of wild‐type nor mutated forms of the protein are involved in the above mentioned changes.