Nitrative and oxidative DNA damage caused by K-ras mutation in mice
Nitrative and oxidative DNA damage caused by K-ras mutation in mice
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K-ras突变引起小鼠的硝基和氧化DNA损伤
DOI：
10.1016/j.bbrc.2011.08.076
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
S.
中科院分区：
文献类型：
--
作者：
Ohnishi;S.
Ras突变在癌变中起重要作用。癌变是由多个基因突变组成的多步骤过程。我们利用条件转基因小鼠研究了DNA损伤在K-ras突变引发的癌变中的作用。免疫组化分析显示，致突变性的8-硝基鸟嘌呤和8-氧-7,8-二氢-2 ' -脱氧鸟嘌呤（8-oxodG）在突变的K-ras引起的腺癌中明显形成。8-硝基鸟嘌呤与iNOS、eNOS、NF-κB、IKK、MAPK、MEK和突变的K-ras共定位，表明致癌的K-ras通过涉及这些分子的信号通路引起额外的DNA损伤。值得注意的是，K-ras突变不仅介导细胞过度增殖，而且介导突变性DNA病变的积累，导致癌变。
Ras mutation is important for carcinogenesis. Carcinogenesis consists of multi-step process with mutations in several genes. We investigated the role of DNA damage in carcinogenesis initiated by K-ras mutation, using conditional transgenic mice. Immunohistochemical analysis revealed that mutagenic 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) were apparently formed in adenocarcinoma caused by mutated K-ras. 8-Nitroguanine was co-localized with iNOS, eNOS, NF-κB, IKK, MAPK, MEK, and mutated K-ras, suggesting that oncogenic K-ras causes additional DNA damage via signaling pathway involving these molecules. It is noteworthy that K-ras mutation mediates not only cell over-proliferation but also the accumulation of mutagenic DNA lesions, leading to carcinogenesis.