Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats. A study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS).
We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual.
Suzuki
Hiroshi
H
Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan. h-suzuki@ina-research.co.jp
Ikeda
Naohiro
N
Kobayashi
Kazuo
K
Terashima
Yukari
Y
Shimada
Yasushi
Y
Suzuki
Takayoshi
T
Hagiwara
Toshiyuki
T
Hatakeyama
Shigeki
S
Nagaoka
Koko
K
Yoshida
Junichi
J
Saito
Yukiko
Y
Tanaka
Jin
J
Hayashi
Makoto
M
D000814:Aniline Compounds / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity; D010655:Phenylenediamines / Q000633:toxicity; D011753:Pyrones / Q000633:toxicity; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014052:Toluidines / Q000633:toxicity; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity; D001559:Benzhydryl Compounds
D000814:Aniline Compounds; D002273:Carcinogens; D004051:Diethylhexyl Phthalate; D008741:Methyl Methanesulfonate; D009153:Mutagens; D009602:Nitrosamines; D010655:Phenylenediamines; D011753:Pyrones; D011804:Quinolines; D014052:Toluidines; D004124:p-Dimethylaminoazobenzene; C011890:kojic acid; C015060:4-chloro-1,2-diaminobenzene; C023622:2-toluidine; C037219:quinoline; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds