title: Evaluation of a repeated-dose liver micronucleus assay with 2,6-dinitrotoluene using young adult rats.
abstract: As part of a collaborative study by the Mammalian Mutagenicity Study Group of the Environmental Mutagen Society of Japan, we examined micronucleus induction in hepatocytes following oral administration of 2,6-dinitrotoluene (2,6-DNT) at 30, 40, and 50mg/kg/day for 14 days or at 20, 30, and 40mg/kg/day for 28 days to young adult male rats. This compound is known to be a rat liver carcinogen. The formation of micronucleated hepatocytes was confirmed to be dose-dependent with statistically significant increases observed in both treatments. In contrast, no statistically significant changes in the percentage of micronucleated immature erythrocytes were observed in any dose group in the bone marrow micronucleus assay. These results indicated that the repeated-dose liver micronucleus assay has the potential to detect genotoxic hepatocarcinogens and can be integrated into general toxicological studies.
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan. Electronic address: t-imamura@ina-research.co.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Koeda
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
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: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otabe
authors.affiliation: Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D003299:Cooperative Behavior; D004136:Dinitrobenzenes / Q000633:toxicity*; 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; D015162:Micronucleus Tests; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects; D012957:Societies, Pharmaceutical
chemical_list: D002273:Carcinogens; D004136:Dinitrobenzenes; C023514:2,6-dinitrotoluene
keywords: 2,6-DNT; Liver carcinogen; Repeated dose liver micronucleus assay