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).
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.
Takasawa
Hironao
H
Mitsubishi Chemical Medience Corporation, 14 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan. Takasawa.Hironao@mg.medience.co.jp
Suzuki
Hiroshi
H
Ogawa
Izumi
I
Shimada
Yasushi
Y
Kobayashi
Kazuo
K
Terashima
Yukari
Y
Matsumoto
Hirotaka
H
Oshida
Keiyu
K
Ohta
Ryo
R
Imamura
Tadashi
T
Miyazaki
Atsushi
A
Kawabata
Masayoshi
M
Minowa
Shigenori
S
Maeda
Akihisa
A
Hayashi
Makoto
M
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
D002273:Carcinogens