title: In vivo mutagenicity of arsenite in the livers of gpt delta transgenic mice.
abstract: While arsenic has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), its mutagenicity has not been fully characterized in experimental animals. The aim of this study was to assess the in vivo mutagenicity of arsenite in C57BL/6J gpt delta mice. Male gpt delta mice were given drinking water containing sodium arsenite for 3 weeks, and the hepatic genome was assayed for mutations 2 weeks later. The gpt mutation assays showed a significant increase in mutation frequency in the liver following arsenite exposure. Sequence analysis revealed that 67% of mutations detected are G:C to A:T transitions and 5% are G:C to T:A transversions in the control group, and arsenite exposure resulted in a markedly higher rate of G:C to T:A transversions (46% of mutations detected). G:C to T:A transversions have been reported to be induced following formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a representative product that results from oxidative DNA damage. We also detected a significant increase in 8-OHdG in the livers of the mice exposed to arsenite. These results demonstrate that arsenite has mutagenicity in vivo and suggest that arsenite induces G:C to T:A transversions through oxidative-stress-induced 8-OHdG formation.
authors: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors: Shota
authors: S
authors: Takumi
authors: Center for Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors: Yasunobu
authors: Y
authors: Aoki
authors: Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors: Tomoharu
authors: T
authors: Sano
authors: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors: Takehiro
authors: T
authors: Suzuki
authors: Biological Safety Research Center, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors: Takehiko
authors: T
authors: Nohmi
authors: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. Electronic address: keikon@nies.go.jp.
authors: Keiko
authors: K
authors: Nohara
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001483:Base Sequence; D002374:Catalase / Q000235:genetics; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation / Q000187:drug effects; D010430:Pentosyltransferases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D018053:Arsenites; D002374:Catalase; D003849:Deoxyguanosine; D029968:Escherichia coli Proteins; D010430:Pentosyltransferases; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; C071962:Gpt protein, E coli; C015001:arsenite
keywords: 8-Hydroxy-2′-deoxyguanosine (8-OHdG); Arsenite; DNA methylation; Mutation; gpt delta mouse