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

Genes and Environment

Hisakazu Sanada³  Shuichi Hamada²  Kenichi Masumura¹  Takehiko Nohmi¹  Hiroyuki Hayashi⁴  Masayuki Hasuko¹  Rie Takashima²  Kazunori Narumi²  Tadashi Noguchi⁵  Tomoyuki Kamigaito⁵ 

[1] Division of Genetics and Mutagenesis, National Institute of Health Sciences;Safety Assessment Department, Mitsubishi Chemical Medience Corporation;Central Research Laboratories, Kaken Pharmaceutical Co., Ltd.;Toxicology Laboratory, Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd.;Japan Bioassay Research Center, Japan Industrial Safety and Health Association

关键词: F344 gpt delta transgenic rat;    nickel subsulfide;    gpt assay;    Spi− assay;   

DOI  :  10.3123/jemsge.34.34

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(67)Cited-By(1)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.

【 授权许可】

Unknown