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To explore combined genotoxic effects of radiation and chemicals, we examined modulating effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting methylating agent, against genotoxicity of γ-radiation. Human lymphoblastoid TK6 cells and its mismatch-deficient derivative, i.e., MT1 cells, were treated with MNNG for 24h before they were exposed to γ-irradiation at a dose of 1.0 Gy, and the resulting genotoxicity was examined. In TK6 cells, the pretreatments with MNNG at low doses suppressed frequencies of the thymidine kinase (TK) gene mutation and micronucleus (MN) formation induced by γ-irradiation and thus the dose responses of TK and MN assays were U-shaped along with the pretreatment doses of MNNG. In contrast, the genotoxic effects of MNNG and γ-irradiation were additive in MT1 cells and the frequencies of TK mutations and MN induction increased along with the doses of MNNG. Apoptosis induced by γ-radiation was suppressed by the pretreatments in TK6 cells, but not in MT1 cells. The expression of p53 was induced and cell cycle was delayed at G2/M phase in TK6, but not in MT1 cells, by the treatments with MNNG. These results suggest that pretreatments of MNNG at low doses suppress genotoxicity of γ-radiation in human cells and also that mismatch repair proteins are involved in the apparent adaptive responses."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004232380372739","@type":"Researcher","foaf:name":[{"@value":"Ayumi Yamamoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232380372740","@type":"Researcher","foaf:name":[{"@value":"Yasuteru 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Nohmi"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13861964"},{"@type":"PISSN","@value":"00275107"}],"prism:publicationName":[{"@value":"Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2011-08","prism:volume":"713","prism:number":"1-2","prism:startingPage":"56","prism:endingPage":"63"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","https://doi.org/10.15223/policy-017","https://doi.org/10.15223/policy-037","https://doi.org/10.15223/policy-012","https://doi.org/10.15223/policy-029","https://doi.org/10.15223/policy-004"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0027510711001382?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0027510711001382?httpAccept=text/plain"}],"createdAt":"2011-06-25","modifiedAt":"2025-12-02","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Methylnitronitrosoguanidine","dc:title":"Methylnitronitrosoguanidine"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Cycle","dc:title":"Cell Cycle"},{"@id":"https://cir.nii.ac.jp/all?q=Adaptation,%20Biological","dc:title":"Adaptation, Biological"},{"@id":"https://cir.nii.ac.jp/all?q=Apoptosis","dc:title":"Apoptosis"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20Mismatch%20Repair","dc:title":"DNA Mismatch Repair"},{"@id":"https://cir.nii.ac.jp/all?q=Thymidine%20Kinase","dc:title":"Thymidine Kinase"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Gamma%20Rays","dc:title":"Gamma Rays"},{"@id":"https://cir.nii.ac.jp/all?q=Mutation","dc:title":"Mutation"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Lymphocytes","dc:title":"Lymphocytes"},{"@id":"https://cir.nii.ac.jp/all?q=Micronuclei,%20Chromosome-Defective","dc:title":"Micronuclei, Chromosome-Defective"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282257081131136","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22241016"},{"@type":"JGN","@value":"JP22241016"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22241016/"}],"notation":[{"@language":"ja","@value":"ＤＮＡポリメラーゼζ（ゼータ）の遺伝的改変による遺伝毒性閾値形成機構に関する研究"},{"@language":"en","@value":"Studies on mechanisms underlying genotoxic thresholds through genetic modification of DNA polymerase zeta"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011145705904128","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Relationship between p53 status and 5-fluorouracil sensitivity in 3 cell lines"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714192733312","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Protective effects of raw and cooked blackcurrant extract on DNA 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