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首页> 外文期刊>Journal of applied toxicology >Organ differences in the impact of p27kip1 deficiency on carcinogenesis induced by N-methyl-N-nitrosourea
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Organ differences in the impact of p27kip1 deficiency on carcinogenesis induced by N-methyl-N-nitrosourea

机译：p27kip1缺乏对N-甲基-N-亚硝基脲致癌作用影响的器官差异

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摘要

To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27+/+ and p27+/- cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis.
机译：为了评估p27对各种器官癌变的影响，将N-甲基-N-亚硝基脲（MNU）（一种直接作用的烷基化剂）给予了p27基因敲除小鼠。每隔20周给每组20-40只具有无效，异源或野生型p27等位基因的雄性和雌性小鼠喝含240ppm MNU的饮用水或蒸馏水，每五个星期一次。然后在第14周和第20周进行组织学评估诱导的增生性病变的发生率和多样性。MNU治疗诱发的各种病变包括前胃癌，前庭和幽门腺的非典型增生和腺癌，鳞状增生和鳞状细胞癌，腺癌和幽门腺，腺瘤和腺癌。十二指肠，胸腺，肝脏，肾脏和脾脏的恶性淋巴瘤和肺泡增生，腺瘤，腺癌和肺部的恶性淋巴瘤。尽管p27基因型在前胃，胃底和幽门腺中的病变发生率没有差异，但与野生型和野生型相比，p27无性型男性的肺泡增生和胸腺恶性淋巴瘤的发生率明显增加。异型动物。此外，在p27 + / +和p27 +/-病例中，在幽门腺和肺的增生性病变中，p27阳性细胞的发生率明显增加。但是，在胸腺的恶性淋巴瘤中未观察到p27阳性细胞的增加。这些发现表明，在受MNU致癌作用影响的所有器官中，p27均不能平等地控制细胞周期。

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