A noncarcinogenic small dose of n-methylnitrosourea enhances colon tumorigenesis in F344 rats
A noncarcinogenic small dose of n-methylnitrosourea enhances colon tumorigenesis in F344 rats
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DOI：
10.1620/tjem.199.43
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发表时间：
2003-01-01
影响因子：
2.2
通讯作者：
Fukaura, Y
中科院分区：
文献类型：
--
作者：
Narisawa, T;Fukaura, Y
在人类粪便中发现了极少量的致癌物，如亚硝基化合物和杂环胺。本研究旨在研究F344大鼠直肠内非致癌性小剂量n-甲基亚硝基脲（0.2mg，每周3次）是否影响直肠内引起的结肠癌。大剂量（2毫克，每周3次）这种致癌物。在第50周，12只接受大剂量治疗2周，然后再接受小剂量治疗30周的大鼠，与23只只接受大剂量治疗2周的大鼠相比，结肠肿瘤产量显著增加：肿瘤发生率为100%对70%，每只大鼠平均肿瘤数为4.3对1.2。12只接受小剂量30周的大鼠未发现肿瘤。结果表明，即使少量的致癌物不足以完成癌变过程，但极少量的致癌物可以参与大剂量致癌物诱导的高危结肠的促瘤作用。需要进一步的研究来阐明这样小剂量的施用是否会诱导初始结肠细胞的表观遗传改变或进一步的遗传改变。
Very small amount of carcinogens such as nitroso compounds and heterocyclic amines has been found in human feces. This study was designed to investigate in F344 rats whether an intrarectal noncarcinogenic small dose of n-methylnitrosourea (0.2mg, 3 times weekly) affects colon carcinogenesis initiated with an intrarectal. large dose (2 mg, 3 times weekly) of this carcinogen. The colon tumor yield at week 50 in 12 rats receiving the large dose for 2 weeks and then the small dose for the next 30 weeks significantly increased as compared to 23 rats receiving only the large dose for 2 weeks: 100% vs. 70% in tumor incidence and 4.3 vs. 1.2 in mean number of tumors per rat. No tumors were found in 12 rats receiving only the small dose for 30 weeks. The results indicate that a very small amount of carcinogens could participate in a tumor-enhancing effect on the high-risk colon induced with a large dose of carcinogens, even though their less amounts insufficient to complete carcinogenesis process. Further study is needed to elucidate if administration of such a small dose could induce epigenetic alterations or further genetic changes in the initiated colonic cells.