Evaluation of the in vivo Mutagenicity of Nickel Subsulfide in the Lung of F344 gpt delta Transgenic Rats Exposed by Intratracheal Instillation: A Collaborative Study for the gpt delta Transgenic Rat Mutation Assay

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  • Kamigaito Tomoyuki
    Japan Bioassay Research Center, Japan Industrial Safety and Health Association
  • Noguchi Tadashi
    Japan Bioassay Research Center, Japan Industrial Safety and Health Association
  • Narumi Kazunori
    Safety Assessment Department, Mitsubishi Chemical Medience Corporation
  • Takashima Rie
    Safety Assessment Department, Mitsubishi Chemical Medience Corporation
  • Hamada Shuichi
    Safety Assessment Department, Mitsubishi Chemical Medience Corporation
  • Sanada Hisakazu
    Central Research Laboratories, Kaken Pharmaceutical Co., Ltd.
  • Hasuko Masayuki
    Division of Genetics and Mutagenesis, National Institute of Health Sciences
  • Hayashi Hiroyuki
    Toxicology Laboratory, Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd.
  • Masumura Kenichi
    Division of Genetics and Mutagenesis, National Institute of Health Sciences
  • Nohmi Takehiko
    Division of Genetics and Mutagenesis, National Institute of Health Sciences

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Description

This study was conducted to evaluate the effectiveness of a transgenic rat mutation assay using F344 gpt delta rats. We investigated the mutagenic potential in the lung of nickel subsulfide (Ni3S2), an insoluble fine-crystalline-metallic compound and a carcinogen in the rodent and human lung. Ni3S2 carcinogenicity has been proposed to act via both genotoxic and non-genotoxic mechanisms. Ni3S2 was intratracheally instilled into male gpt delta rats at doses of 0.5 and 1 mg/animal once a week for four weeks; these doses of Ni3S2 are high enough to induce inflammation in the lung. Following a period of 28 and 90 days after the first administration, the gpt mutant frequencies (MFs) in lung were determined in four independent laboratories, and Spi− selection for larger deletion mutations was done in one laboratory. The gpt MFs of the rats treated with Ni3S2 were not increased: all four laboratories obtained similar results with no statistical differences. The Spi− MFs were also not increased by exposure to Ni3S2. These results indicate that intratracheally instilled Ni3S2 is non-mutagenic in the lung of gpt delta transgenic rats; however, whether Ni3S2 is non-mutagenic in the lung or it induces mutations which are not detectable by transgenic rodent mutation assays requires further investigation.<br>

Journal

  • Genes and Environment

    Genes and Environment 34 (1), 34-44, 2012

    The Japanese Environmental Mutagen and Genome Society

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