Mutagenic Specificity of N-Nitrosotaurocholic Acid in supF Shuttle Vector Plasmids
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概要
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The mutagenic specificity of N-nitrosotaurocholic acid (NO-TCA) in human cells was investigated using supF shuttle vector plasmids. The plasmids pMY 189 were treated with NO-TCA in vitro and introduced into normal fibroblasts (WI38-VA13) and nucleotide excision repair (NER)-deficient cells (XP2OS(SV)) for replication. The background mutation frequency of the supF gene was 4.1×10^<-4> and 2.0×10^<-4> after replication in normal and NER-deficient cells, respectively. The mutation frequency increased 5 and 15 times in normal and NER-deficient cells, respectively, after the treatment of the plasmid with 50mg/mL of NO-TCA. The higher mutation frequency in NER-deficient cells indicates that the DNA damage induced by NO-TCA is repaired by NER. Base sequence analysis of 101 and 94 plasmids with mutations in the supF gene propagated in normal and NER-deficient cells, respectively, revealed that the majority of the mutations were base substitutions (about 89 and 90%) and the rest were deletions and insertions (about 11 and 10%) in both cell lines. About half of the mutant plasmids contained a single base substitution. Of the single base substitutions, the most frequent mutations were G:C to A:T transitions (about 37 and 36%), followed by G:C to C:G transversions (about 31 and 28%) in both cell lines. The mutations were not distributed randomly but were located at several hot spots in the supF gene, and almost all hot spots were at G:C sites. These observations accord with previous findings that NO-TCA forms DNA adducts with dC and induces G:C to A:T base substitution in Salmonella typhimurium TA100.
- 日本環境変異原学会の論文
- 2009-02-20
著者
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TOTSUKA Yukari
Cancer Prevention Division, National Cancer Center Research Institute
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WAKABAYASHI Keiji
Cancer Prevention Division, National Cancer Center Research Institute
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Wakabayashi Keiji
Cancer Prevention Basic Research Project National Cancer Center Research Institute
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Totsuka Yukari
Cancer Prevention Basic Research Project National Cancer Center Research Institute
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Kawanishi Masanobu
Environmental Genetics Laboratory, Frontier Science Innovation Center and Department of Biology, Gra
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Yagi Takashi
Environmental Genetics Laboratory, Frontier Science Innovation Center and Department of Biology, Gra
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NISHIMURA Koichi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute
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Wakabayashi K
Cancer Prevention Division National Cancer Center Research Institute
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Nishida Hiroshi
Environmental Genetics Laboratory, Frontier Science Innovation Center and Graduate School of Science
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Wakabayashi Keiji
愛知県がんセンター研究所
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Yagi Takashi
Environmental Genetics Laboratory Frontier Science Innovation Center And Graduate School Of Science
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Wakabayashi K
Cancer Prevention Basic Research Project National Cancer Center Research Institute
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Kawanishi Masanobu
Environmental Genetics Laboratory Frontier Science Innovation Center Osaka Prefecture University
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Kawanishi Masanobu
Environmental Genetics Laboratory Frontier Science Innovation Center And Department Of Biology Gradu
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Totsuka Yukari
Division Of Cancer Development System National Cancer Center Research Institute
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Wakabayashi Keiji
Department Of Food & Nutritional Science Graduate School Of Nutrition & Environmental Scienc
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Yagi Takashi
Environmental Genetics Laboratory Frontier Science Innovation Center Osaka Prefecture University
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Nishimura Koichi
Cancer Prevention Basic Research Project National Cancer Center Research Institute
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Yagi Takashi
Environmental Genetics Laboratory Frontier Science Innovation Center And Department Of Biology Gradu
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Nishida Hiroshi
Environmental Genetics Laboratory Frontier Science Innovation Center And Graduate School Of Science
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Yagi Takashi
Environmental Genetics Laboratory, Frontier Science Innovation Center, Osaka Prefecture University
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