title: Repeated-dose liver micronucleus assay: an investigation with 2-nitropropane, a hepatocarcinogen.
abstract: The utility of the repeated-dose liver micronucleus (RDLMN) assay in the detection of a genotoxic hepatocarcinogen was evaluated. In this paper, a rat hepatocarcinogen, 2-nitropropane (2-NP), was administered orally to young adult rats for 14 and 28 days without a partial hepatectomy or a mitogen, and the micronucleus induction in liver was examined using a simple method to isolate hepatocytes. In addition, a bone marrow micronucleus assay was conducted concomitantly. The frequency of micronucleated hepatocytes induced by 2-NP increased significantly in both the 14- and 28-day repeated-dose studies, while the bone marrow micronucleus assays were negative in each study. These results indicate that the RDLMN assay is useful for detecting a genotoxic hepatocarcinogen that is negative in bone marrow micronucleus assays and is a suitable in vivo genotoxicity test method for integration into a repeated-dose general toxicity study.
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. Electronic address: kawakami.sd@om.asahi-kasei.co.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakami
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Araki
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kusuoka
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Takahashi
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: Laboratory for Safety Assessment & ADME, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsurui
mesh_terms: D000284:Administration, Oral; 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; 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; D009595:Nitroparaffins / Q000633:toxicity*; D009928:Organ Specificity; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects; D012957:Societies, Pharmaceutical
chemical_list: D002273:Carcinogens; D009595:Nitroparaffins; C016617:2-nitropropane; D011407:Propane
keywords: 2-Nitropropane; Bone marrow micronucleus assay; Hepatocarcinogen; Liver micronucleus assay; Repeated-dose toxicity study