Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon.

Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon.
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DOI:
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发表时间:
1996-11
期刊:
影响因子:
11.2
通讯作者:
M. Risio;M. Lipkin;H. Newmark;Kang Yang;F. Rossini;V. Steele;C. Boone;G. Kelloff
M. Risio;M. Lipkin;H. Newmark;Kang Yang;F. Rossini;V. Steele;C. Boone;G. Kelloff
中科院分区:
医学1区
文献类型:
--
作者:
M. Risio;M. Lipkin;H. Newmark;Kang Yang;F. Rossini;V. Steele;C. Boone;G. Kelloff

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在这项研究中,给小鼠喂食西式饮食(WD)持续两年,不含任何化学致癌物,导致出现肉眼可见的结肠病变,组织学分类为异型增生的隐窝和局灶性增生,伴或不伴非典型细胞核。为了更好地了解早期生物学事件的结肠肿瘤的发展,大体正常的结肠粘膜进行了调查,有丝分裂和凋亡的结肠上皮细胞,非典型有丝分裂,和非典型细胞核进行了研究。给幼鼠喂食WD后,在结肠隐窝的基部和中间部分观察到有丝分裂活性的显著和短暂的增加。这伴随着结肠上皮细胞凋亡的弥漫性激活。在啮齿动物寿命中期,给予WD和对照饲料后,啮齿动物结肠隐窝中部区域的凋亡上皮细胞显著减少;随后是含有非典型细胞核的上皮细胞群扩增,并出现上述肉眼病变。在这一系列事件中,长时间喂食WD小鼠会产生单隐窝发育不良病变和局灶性增生,提示肿瘤发生。
In this study, feeding Western-style diets (WDs) to mice for a duration of two years without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dysplastic crypts and focal hyperplasias with or without atypical nuclei. To better understand early biological events contributing to the development of colonic neoplasia, grossly normal colonic mucosa was investigated; mitotic and apoptotic colonic epithelial cells, atypical mitosis, and atypical nuclei were studied. A significant and transient increase of mitotic activity in the basal and intermediate portions of the colonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epithelial cells. In the middle of the rodents' life span, after administration of both the WDs and control diet, the rodents developed a marked depletion of apoptotic epithelial cells in the mid-region of the colonic crypts; this was followed by the expansion of an epithelial cell population containing atypical nuclei, and the emergence of the gross lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced single-crypt dysplastic lesions and focal hyperplasias indicative of tumorigenesis.