title: A novel metabolic activation associated with glutathione in dimethylmonothioarsinic acid (DMMTA(V))-induced toxicity obtained from in vitro reaction of DMMTA(V) with glutathione.
abstract: The purpose of the present study was to elucidate the metabolic processing of dimethylmonothioarsinic acid (DMMTA(V)), which is a metabolite of inorganic arsenic and has received a great deal of attention recently due to its high toxicity. The metabolites produced from an in vitro reaction with GSH were analyzed by high performance liquid chromatography-time of flight mass spectrometer (HPLC-TOFMS), HPLC with a photodiode array detector (PDA), and also gas chromatography-mass spectrometry (GC-MS) and GC with a flame photometric detector (FPD). The reaction of dimethylarsinic acid (DMA(V)) with GSH did not generate DMA(V)-SG but did generate dimethylarsinous acid (DMA(III)) or DMA(III)-SG. On the contrary, we confirmed that the reaction of DMMTA(V) with GSH directly produced the stable complex of DMMTA(V)-SG without reduction through a trivalent dimethylated arsenic such as DMA(III) and DMA(III)-SG. Furthermore, the present study suggests the production of hydrogen sulfide (H2S) and dimethylmercaptoarsine (DMA(III)-SH), a trivalent dimethylated arsenic, as well as DMA(III) and DMA(III)-SG in the decomposition process of DMMTA(V)-SG. These results indicate that the toxicity of DMMTA(V) depends not only on the formation of DMA(III) but also on at least those of H2S and DMA(III)-SH.
authors.affiliation: Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Chiba 274-8555, Japan; Criminal Investigation Laboratory, Metropolitan Police Department, Tokyo 100-8929, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Chiba 274-8555, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Laboratory of Molecular Chemistry, Nihon University School of Pharmacy, Chiba 274-8555, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Miura
authors.affiliation: Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Chiba 274-8555, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.affiliation: Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Chiba 274-8555, Japan. Electronic address: yamanaka.kenzo@nihon-u.ac.jp.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Department of Medical Risk Management, Graduate School of Risk and Crisis Management, Chiba Institute of Science, Chiba 288-0025, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hata
authors.affiliation: Department of Hygiene and Preventive Medicine, School of Medicine, Showa University, 142-8555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Research Center for Occupational Poisoning, Kansai Rosai Hospital, Hyogo 660-8511, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Preventive Medicine and Environmental Health, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Ginji
authors.initials: G
authors.lastname: Endo
mesh_terms: D065767:Activation, Metabolic / Q000187:drug effects*; D001152:Arsenicals / Q000737:chemistry; D002101:Cacodylic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000737:chemistry*; D006862:Hydrogen Sulfide / Q000032:analysis; D013058:Mass Spectrometry; D012996:Solutions; D013997:Time Factors; D001149:Arsenates
chemical_list: D001152:Arsenicals; D002101:Cacodylic Acid; D005978:Glutathione; D006862:Hydrogen Sulfide; D012996:Solutions; C518667:dimethylmonothioarsinic acid; D001149:Arsenates
keywords: Dimethylarsinic acid; Dimethylarsinous acid; Dimethylmercaptoarsine; Dimethylmonothioarsinic acid