First Author | Ohnishi S | Year | 2011 |
Journal | Biochem Biophys Res Commun | Volume | 413 |
Issue | 2 | Pages | 236-40 |
PubMed ID | 21875576 | Mgi Jnum | J:177529 |
Mgi Id | MGI:5295346 | Doi | 10.1016/j.bbrc.2011.08.076 |
Citation | Ohnishi S, et al. (2011) Nitrative and oxidative DNA damage caused by K-ras mutation in mice. Biochem Biophys Res Commun 413(2):236-40 |
abstractText | 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-kappaB, 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. |