title: 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.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saito
authors.forename: Noboru
authors.initials: N
authors.lastname: Suzuki
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D011905:Genes, ras; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000235:genetics*
chemical_list: C095838:8-nitroguanine; C024829:8-hydroxyguanine; D006147:Guanine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse