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Evaluation of the repeated-dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats: summary of the collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) - Mammalian Mutagenicity Study Group (MMS).
Hamada, Shuichi; Ohyama, Wakako; Takashima, Rie; Shimada, Keisuke; Matsumoto, Kazumi; Kawakami, Satoru; Uno, Fuyumi; Sui, Hajime; Shimada, Yasushi; Imamura, Tadashi; Matsumura, Shoji; Sanada, Hisakazu; Inoue, Kenji; Muto, Shigeharu; Ogawa, Izumi; Hayashi, Aya; Takayanagi, Tomomi; Ogiwara, Yosuke; Maeda, Akihisa; Okada, Emiko; Terashima, Yukari; Takasawa, Hironao; Narumi, Kazunori; Wako, Yumi; Kawasako, Kazufumi; Sano, Masaki; Ohashi, Nobuyuki; Morita, Takeshi; Kojima, Hajime; Honma, Masamitsu; Hayashi, Makoto.
Affiliation
  • Hamada S; LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan; National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-0098, Japan; University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Electronic address: Hamada.Shuuichi@mh.medie
  • Ohyama W; Yakult Honsha Co., Ltd., 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
  • Takashima R; LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
  • Shimada K; Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka-shi, Osaka 532-8514, Japan.
  • Matsumoto K; Astellas Research Technologies Co., Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka-shi, Osaka 532-8514, Japan.
  • Kawakami S; Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
  • Uno F; Public Interest Incorporated Foundation, Biosafety Research Center, 582-2 Shioshinden, Iwata-shi, Shizuoka 437-1213, Japan.
  • Sui H; Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa 257-8523, Japan.
  • Shimada Y; Hokko Chemical Industry Co., Ltd., Mitsui Building Annex No.2 4-20, Nihonbashi Hongoku-cho 4-chome, Chuo-ku, Tokyo 103-8341, Japan.
  • Imamura T; Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
  • Matsumura S; Kao Corporation, 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
  • Sanada H; Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda-shi, Shizuoka 426-8646, Japan.
  • Inoue K; Maruho Co., Ltd., 93 Awata-cho, Chudoji, Shimogyo-ku, Kyoto 600-8815, Japan.
  • Muto S; Mitsubishi Tanabe Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan.
  • Ogawa I; Nissan Chemical Industries, Ltd., 1470 Shiraoka, Shiraoka-shi, Saitama 349-0294, Japan.
  • Hayashi A; Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura-cho, Kagoshima-shi, Kagoshima 891-1394, Japan.
  • Takayanagi T; Suntory Business Expert Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
  • Ogiwara Y; Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
  • Maeda A; Toray Industries Inc., 6-10-1 Tebiro, Kamakura-shi, Kanagawa 248-8555, Japan.
  • Okada E; Yakult Honsha Co., Ltd., 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
  • Terashima Y; Kissei Pharmaceutical Co., Ltd., 2320-1 Maki, Hotaka, Azumino-shi, Nagano 399-8305, Japan.
  • Takasawa H; LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
  • Narumi K; Yakult Honsha Co., Ltd., 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
  • Wako Y; LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
  • Kawasako K; LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
  • Sano M; Public Interest Incorporated Foundation, Biosafety Research Center, 582-2 Shioshinden, Iwata-shi, Shizuoka 437-1213, Japan.
  • Ohashi N; Public Interest Incorporated Foundation, Biosafety Research Center, 582-2 Shioshinden, Iwata-shi, Shizuoka 437-1213, Japan.
  • Morita T; National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-0098, Japan.
  • Kojima H; National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-0098, Japan.
  • Honma M; National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-0098, Japan.
  • Hayashi M; Public Interest Incorporated Foundation, Biosafety Research Center, 582-2 Shioshinden, Iwata-shi, Shizuoka 437-1213, Japan.
Article in En | MEDLINE | ID: mdl-25892619
The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinogens / Hazardous Substances / Micronucleus Tests / Hepatocytes / Gastrointestinal Tract / Liver Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Country/Region as subject: Asia Language: En Journal: Mutat Res Genet Toxicol Environ Mutagen Year: 2015 Document type: Article Country of publication: Países Bajos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinogens / Hazardous Substances / Micronucleus Tests / Hepatocytes / Gastrointestinal Tract / Liver Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Female / Humans / Male Country/Region as subject: Asia Language: En Journal: Mutat Res Genet Toxicol Environ Mutagen Year: 2015 Document type: Article Country of publication: Países Bajos