{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360002220677301632.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/ijms150712543"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/1422-0067/15/7/12543/pdf"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Cellular Levels of 8-Oxoguanine in either DNA or  the Nucleotide Pool Play Pivotal Roles in Carcinogenesis  and Survival of Cancer Cells"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation of the DNA guanine base. MTH1, also known as NUDT1, with 8-oxo-dGTP hydrolyzing activity, 8-oxoguanine DNA glycosylase (OGG1) an 8-oxoG DNA glycosylase, and MutY homolog (MUTYH) with adenine DNA glycosylase activity, minimize the accumulation of 8-oxoG in DNA; deficiencies in these enzymes increase spontaneous  and induced tumorigenesis susceptibility. However, different tissue types have different tumorigenesis susceptibilities. These can be reversed by combined deficiencies in the defense systems, because cell death induced by accumulation of 8-oxoG in DNA is dependent on MUTYH, which can be suppressed by MTH1 and OGG1. In cancer cells encountering high oxidative stress levels, a high level of 8-oxo-dGTP accumulates in the nucleotide pool, and cells therefore express increased levels of MTH1 in order to eliminate 8-oxo-dGTP. Suppression of MTH1 may be an efficient strategy for killing cancer cells; however, because MTH1 and OGG1 protect normal tissues from oxidative-stress-induced cell death, it is important that MTH1 inhibition does not increase the risk of healthy tissue degeneration.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1030003658328311425","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30180350"},{"@type":"NRID","@value":"1000030180350"},{"@type":"ORCID","@value":"0000-0002-6739-242X"},{"@type":"NRID","@value":"9000364829296"},{"@type":"NRID","@value":"9000002585202"},{"@type":"NRID","@value":"9000413235732"},{"@type":"NRID","@value":"9000411107033"},{"@type":"NRID","@value":"9000412104416"},{"@type":"NRID","@value":"9000020134847"},{"@type":"NRID","@value":"9000018719197"},{"@type":"NRID","@value":"9000016851660"},{"@type":"NRID","@value":"9000301734825"},{"@type":"NRID","@value":"9000007053809"},{"@type":"NRID","@value":"9000391978172"},{"@type":"NRID","@value":"9000261652734"},{"@type":"NRID","@value":"9000004128331"},{"@type":"NRID","@value":"9000252815071"},{"@type":"NRID","@value":"9000399595394"},{"@type":"NRID","@value":"9000016430357"},{"@type":"NRID","@value":"9000397978344"},{"@type":"NRID","@value":"9000315683321"},{"@type":"NRID","@value":"9000380962510"},{"@type":"NRID","@value":"9000283422474"},{"@type":"NRID","@value":"9000001414005"},{"@type":"NRID","@value":"9000022913337"},{"@type":"NRID","@value":"9000391623596"},{"@type":"NRID","@value":"9000001738142"},{"@type":"NRID","@value":"9000398127830"},{"@type":"NRID","@value":"9000315683309"},{"@type":"NRID","@value":"9000410922652"},{"@type":"NRID","@value":"9000347048075"},{"@type":"NRID","@value":"9000391986574"},{"@type":"NRID","@value":"9000241868305"},{"@type":"NRID","@value":"9000347049079"},{"@type":"NRID","@value":"9000259821739"},{"@type":"NRID","@value":"9000001900409"},{"@type":"NRID","@value":"9000364834403"},{"@type":"NRID","@value":"9000412104493"},{"@type":"NRID","@value":"9000001738546"},{"@type":"NRID","@value":"9000364834394"},{"@type":"NRID","@value":"9000260193256"},{"@type":"NRID","@value":"9000347048576"},{"@type":"NRID","@value":"9000391986176"},{"@type":"NRID","@value":"9000253202864"},{"@type":"NRID","@value":"9000287361239"},{"@type":"NRID","@value":"9000001109246"},{"@type":"NRID","@value":"9000107363236"},{"@type":"NRID","@value":"9000413235739"},{"@type":"NRID","@value":"9000260188629"},{"@type":"NRID","@value":"9000413235758"},{"@type":"NRID","@value":"9000408904052"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0171811"}],"foaf:name":[{"@value":"Yusaku Nakabeppu"}],"jpcoar:affiliationName":[{"@value":"Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, and Research Center for Nucleotide Pool, Kyushu University,  3-1-1 Maidashi, Fukuoka 812-8582, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14220067"}],"prism:publicationName":[{"@value":"International Journal of Molecular Sciences"}],"dc:publisher":[{"@value":"MDPI 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tumours"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825893760716160","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Persistent oxidative stress in cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894173902336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894922356224","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"MUTYH-associated polyposis (MAP)"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895309369344","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Origins of Spontaneous Mutations: Specificity and Directionality of Base-Substitution, Frameshift, and Sequence-Substitution Mutageneses"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895483941888","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895734790656","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mutator Phenotype of MUTYH-null Mouse Embryonic Stem Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825896064161152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368231480320","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Deficiencies in Mouse <b>\n                     <i>Myh</i>\n                  </b> and <b>\n                     <i>Ogg1</i>\n                  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