title: Assessment of methyl methanesulfonate using the repeated-dose liver micronucleus assay in young adult rats.
abstract: A repeated-dose liver micronucleus assay using young adult rats was conducted with methyl methanesulfonate (MMS) as a part of a collaborative study supported by the Collaborative Study Group for the Micronucleus Test/the Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. MMS is a classical DNA-reactive carcinogen, but it is not a liver carcinogen. In the first experiment (14-day study), MMS was administered per os to 6-week-old male Crl:CD (SD) rats every day for 14 days at a dose of 12.5, 25, or 50mg/kg/day. In the second experiment (28-day study), 6-week-old male SD rats were treated with MMS at 7.5, 15, or 30mg/kg/day for 28 days, because the highest dose used in the 14-day study (50mg/kg/day) caused mortality. Hepatocyte and bone marrow cell specimens were prepared on the day after the final dose. The frequency of micronucleated hepatocytes (MNHEPs) in the liver and that of micronucleated immature erythrocytes (MNIMEs) in the bone marrow were evaluated. Exposure to 50mg/kg/day MMS for 14 days resulted in an increased frequency of MNHEPs, but MMS had no effect on the frequency of MNHEPs in the rats exposed to the chemical for 28 days at doses up to 30mg/kg/day. MMS induced MNIMEs production at doses of 25 and 50mg/kg/day in the 14-day study and at doses of 15 and 30mg/kg/day in the 28-day study. Overall, the effect of MMS on the frequency of MNHEPs was considered to be equivocal.
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan. Electronic address: Muto.Shigeharu@mf.mt-pharma.co.jp.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Muto
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Wako
authors.affiliation: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwase
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Uno
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D003299:Cooperative Behavior; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D015162:Micronucleus Tests; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects* / Q000473:pathology; D012957:Societies, Pharmaceutical
chemical_list: D002273:Carcinogens; D008741:Methyl Methanesulfonate
keywords: Liver; Methyl methanesulfonate; Micronucleus; Repeated-dose