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Publication : Nitrative and oxidative DNA damage caused by K-ras mutation in mice.

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.
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