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

Abstract

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.

• Authors: Shiho Ohnishi, Hiromitsu Saito, Noboru Suzuki, Ning Ma, Yusuke Hiraku, Mariko Murata, Shosuke Kawanishi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 413 Issue 2 Pg. 236-40 (Sep 23 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21875576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 8-nitroguanine
• 8-hydroxyguanine
• Guanine
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Adenocarcinoma (genetics, metabolism)
• Animals
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics, metabolism)
• DNA Damage (genetics)
• Genes, ras
• Guanine (analogs & derivatives, metabolism)
• Mice
• Mutation
• Nitric Oxide Synthase Type II (biosynthesis)
• Oxidative Stress (genetics)