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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 <jats:italic>in vivo<\/jats:italic> mutagenicity of 1,2\u2010DCP and DCM, alone or combined, in the livers of <jats:italic>gpt<\/jats:italic> delta rats. Six\u2010week\u2010old male F344 <jats:italic>gpt<\/jats:italic> delta rats were treated with 1,2\u2010DCP, DCM or 1,2\u2010DCP\u2009+\u2009DCM by oral administration for 4\u2009weeks at the dose (200\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> body weight 1,2\u2010DCP and 500\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> body weight DCM) used in the carcinogenesis study performed by the National Toxicology Program. <jats:italic>In vivo<\/jats:italic> mutagenicity was analyzed by <jats:italic>gpt<\/jats:italic> mutation\/Spi<jats:sup>\u2212<\/jats:sup> 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\u2010DCP and DCM, were analyzed by quantitative polymerase chain reaction and western blotting. <jats:italic>Gpt<\/jats:italic> and Spi<jats:sup>\u2212<\/jats:sup> mutation frequencies were not increased by 1,2\u2010DCP 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\u2010DCP, DCM and 1,2\u2010DCP\u2009+\u2009DCM had no significant impact on mutagenicity in the livers of <jats:italic>gpt<\/jats:italic> delta rats under our experimental conditions. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3416","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T20:12:44Z","timestamp":1480363964000},"page":"683-691","source":"Crossref","is-referenced-by-count":7,"title":["Lack of <i>in vivo<\/i> mutagenicity of 1,2\u2010dichloropropane and dichloromethane in the livers of <i>gpt<\/i> delta rats administered singly or in combination"],"prefix":"10.1002","volume":"37","author":[{"given":"Tadashi","family":"Hirata","sequence":"first","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"},{"name":"Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy Showa University  1\u20105\u20108 Hatanodai, Shinagawa Tokyo 142\u20108555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Man","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun\u2010ichi","family":"Akagi","sequence":"additional","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isamu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"},{"name":"Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences Gifu University  1\u20101, Yanagido Gifu 501\u20101193 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyoshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences Gifu University  1\u20101, Yanagido Gifu 501\u20101193 Japan"},{"name":"National Institute of Health Science Biological Safety Research Center  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Pathology, Biological Safety Research Center National Institute of Health Sciences  1\u201018\u20101, Kamiyoga, Setagaya\u2010ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2850150409"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70316-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(89)90003-1"},{"key":"e_1_2_7_5_1","first-page":"1915","article-title":"Mutagenicity of pesticides containing 1,3\u2010dichloropropene","volume":"37","author":"De Lorenzo F","year":"1977","journal-title":"Cancer Res."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550100602"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2850100502"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050589"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(94)90050-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00020a008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.929875"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.10152"},{"key":"e_1_2_7_13_1","first-page":"251","article-title":"Dichloromethane. 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