title: Repeated-dose liver and gastrointestinal tract micronucleus assays for quinoline in rats.
abstract: Repeated-dose liver, bone marrow, and gastrointestinal tract micronucleus assays that use young adult rats were evaluated in a collaborative study that was organized by the Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. A genotoxic hepatocarcinogen quinoline was orally administered to independent groups of five Crl:CD (SD) male rats at doses of 30, 60 and 120mg/kg for 14 days and at doses of 15, 30 and 60mg/kg for 28 days. After treatment, the livers were harvested and hepatocytes were isolated by collagenase treatment. The frequency of micronucleated hepatocytes (MNHEPs) increased significantly in both the 14- and 28-day repeated dose studies. However, the frequency of micronucleated cells did not increase in the bone marrow, stomach or colon cells, which were not quinoline-induced carcinogenic target organs in the rats. These results indicate that a repeated-dose liver micronucleus (RDLMN) assay using young adult rats is capable of detecting the genotoxicity of quinoline at the target organ of carcinogenicity. The protocol may also permit the integration of the genotoxic endpoint into general repeated-dose toxicity studies. Furthermore, we elucidated that conducting the micronucleus assay in multiple organs could potentially assess organ specificity.
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan. Electronic address: f-uno@anpyo.or.jp.
authors.forename: Fuyumi
authors.initials: F
authors.lastname: Uno
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Fukumuro
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Natsume
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Oba
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Akahori
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Masumori
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Takami
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: LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Kougo
authors.affiliation: Yakult Honsha Co., Ltd. 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Ohyama
authors.affiliation: Yakult Honsha Co., Ltd. 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Narumi
authors.affiliation: Yakult Honsha Co., Ltd. 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Fujiishi
authors.affiliation: Yakult Honsha Co., Ltd. 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Okada
authors.affiliation: Public Interest Incorporated Foundation, Biosafety Research Center (BSRC), 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
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; D041981:Gastrointestinal Tract / Q000187:drug effects*; 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; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects; D012957:Societies, Pharmaceutical
chemical_list: D002273:Carcinogens; D011804:Quinolines; C037219:quinoline
keywords: Bone marrow; Gastrointestinal tract; Liver micronucleus assay; Quinoline; Repeated-dose toxicity study