Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.
Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.
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DOI：
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发表时间：
1997-06
期刊：
影响因子：
11.2
通讯作者：
K. Sakumi;A. Shiraishi;S. Shimizu;T. Tsuzuki;T. Ishikawa;M. Sekiguchi
中科院分区：
文献类型：
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作者：
K. Sakumi;A. Shiraishi;S. Shimizu;T. Tsuzuki;T. Ishikawa;M. Sekiguchi
基因靶向法获得o6 -甲基鸟嘌呤- dna甲基转移酶MGMT基因缺陷的小鼠[Tsuzuki et al., chinese journal of oncology ., 17: 1215-1220, 1996]。这些MGMT-/-小鼠对烷基化致癌物甲基亚硝基脲最为敏感；给6周龄小鼠不同剂量的甲基亚硝基脲，测定第30天的存活率，MGMT-/-和MGMT+/+小鼠的ld50分别为20和240 mg/kg体重。MGMT+/-小鼠的抗性与MGMT+/+小鼠相同，但当两种基因型小鼠暴露于相对高剂量的甲基亚硝基脲时，其存活时间存在一定差异。暴露于2.5 mg/kg体重剂量的甲基亚硝基脲的MGMT-/-小鼠发生大量胸腺淋巴瘤和肺腺瘤。在相同剂量的药物照射下，MGMT+/+和MGMT+/-小鼠没有或很少发生肿瘤。DNA修复甲基转移酶蛋白似乎保护这些小鼠免受甲基亚硝基源诱导的肿瘤发生。
Gene targeting was used to obtain mice defective in the MGMT gene, encoding O6-methylguanine-DNA methyltransferase [Tsuzuki et al., Carcinogenesis (Lond.), 17: 1215-1220, 1996]. These MGMT-/- mice were most sensitive to the alkylating carcinogen, methylnitrosourea; when varied doses of methylnitrosourea were administered to 6-week-old mice and survivals at the 30th day were determined, LD50s of MGMT-/- and MGMT+/+ mice were 20 and 240 mg/kg of body weight, respectively. MGMT+/- mice were as resistant as MGMT+/+ mice, but some difference in survival time was noted when the two genotypes of mice were exposed to a relatively high dose of methylnitrosourea. A large number of thymic lymphomas, as well as lung adenomas, occurred in MGMT-/- mice exposed to methylnitrosourea at a dose of 2.5 mg/kg of body weight. In case of exposure to the same dose of drug, no or few tumors occurred in the MGMT+/+ and MGMT+/- mice. It appears that the DNA repair methyltransferase protein protected these mice from methylnitrosourea-induced tumorigenesis.