title: Lack of in vivo mutagenicity of 1,2-dichloropropane and dichloromethane in the livers of gpt delta rats administered singly or in combination.
abstract: 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative agents associated with the development of cholangiocarcinoma in employees working in printing plant in Osaka, Japan. However, few reports have demonstrated an association between these agents and cholangiocarcinoma in rodent carcinogenicity studies. Moreover, the combined effects of these compounds have not been fully elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2-DCP and DCM, alone or combined, in the livers of gpt delta rats. Six-week-old male F344 gpt delta rats were treated with 1,2-DCP, DCM or 1,2-DCP + DCM by oral administration for 4 weeks at the dose (200 mg kg-1body weight 1,2-DCP and 500 mg kg-1body weight DCM) used in the carcinogenesis study performed by the National Toxicology Program. In vivo mutagenicity was analyzed by gpt mutation/Spi-assays in the livers of rats. In addition, gene and protein expression of CYP2E1 and GSTT1, the major enzymes responsible for the genotoxic effects of 1,2-DCP and DCM, were analyzed by quantitative polymerase chain reaction and western blotting. Gpt and Spi-mutation frequencies were not increased by 1,2-DCP and/or DCM in any group. Additionally, there were no significant changes in the gene and protein expression of CYP2E1 and GSTT1 in any group. These results indicated that 1,2-DCP, DCM and 1,2-DCP + DCM had no significant impact on mutagenicity in the livers of gpt delta rats under our experimental conditions. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.|Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Akagi
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1, Yanagido, Gifu, 501-1193, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Suzuki
authors.affiliation: Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1, Yanagido, Gifu, 501-1193, Japan.|National Institute of Health Science, Biological Safety Research Center, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity*; D029968:Escherichia coli Proteins / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008752:Methylene Chloride / Q000633:toxicity*; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D010430:Pentosyltransferases / Q000235:genetics*; D017354:Point Mutation; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D011916:Rats, Inbred F344; D055647:Rats, Transgenic
chemical_list: D004785:Environmental Pollutants; D029968:Escherichia coli Proteins; D008752:Methylene Chloride; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; C004765:propylene dichloride; D011407:Propane
keywords: 1,2-dicloropropane; dichloromethane; gpt delta rat; in vivo mutagenicity; liver