title: Evaluation of a liver micronucleus assay in young rats (IV): a study using a double-dosing/single-sampling method by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS).
abstract: A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
authors.affiliation: Mitsubishi Chemical Medience Corporation, 14 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan. Takasawa.Hironao@mg.medience.co.jp
authors.forename: Hironao
authors.initials: H
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Izumi
authors.initials: I
authors.lastname: Ogawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Terashima
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Keiyu
authors.initials: K
authors.lastname: Oshida
authors.forename: Ryo
authors.initials: R
authors.lastname: Ohta
authors.forename: Tadashi
authors.initials: T
authors.lastname: Imamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawabata
authors.forename: Shigenori
authors.initials: S
authors.lastname: Minowa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Maeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000367:Age Factors; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens