<i>In vivo</i> genotoxicity of 1-methylnaphthalene from comprehensive toxicity studies with B6C3F1 <i>gpt</i> delta mice

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  • Jin Meilan
    Division of Pathology, National Institute of Health Sciences
  • Kijima Aki
    Division of Pathology, National Institute of Health Sciences
  • Suzuki Yuta
    Division of Pathology, National Institute of Health Sciences
  • Hibi Daisuke
    Division of Pathology, National Institute of Health Sciences
  • Ishii Yuji
    Division of Pathology, National Institute of Health Sciences
  • Nohmi Takehiko
    Sciences of Genome Safety, National Institute of Health Sciences
  • Nishikawa Akiyoshi
    Biological Safety Research Center, National Institute of Health Sciences
  • Ogawa Kumiko
    Division of Pathology, National Institute of Health Sciences
  • Umemura Takashi
    Division of Pathology, National Institute of Health Sciences

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  • In vivo genotoxicity of 1-methylnaphthalene from comprehensive toxicity studies with B6C3F1 gpt delta mice

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Abstract

1-Methylnaphthalene (1-MN), a constituent of the polycyclic aromatic hydrocarbons (PAHs), is a lung carcinogen in mice. However, conventional genotoxicity tests such as the Ames test and sister chromatid exchange (SCE) test have yielded equivocal results. In the present study, the in vivo genotoxicity of 1-methylnaphthalene (1-MN) together with its toxicological profile was investigated in a 13-week repeated dose toxicity study of 1-MN using B6C3F1 gpt delta mice. In the serum biochemistry, significant increases in AST and ALP were observed in males of the 0.15% 1-MN group. From histopathological examination, the incidence of single cell necrosis in the liver was significantly increased in males of the 0.15% 1-MN group; however, no changes were observed in the lungs, the target organ of 1-MN. In an in vivo mutation assay, no changes in mutant frequencies of gpt and red/gam (Spi-) in lung DNA of 1-MN treated mice were observed at 13 weeks. In addition, there were no significant differences in the proliferating cell nuclear antigen (PCNA)-positive ratios in bronchiolar epithelial cells among the groups for either sex. These results suggest that 1-MN at a carcinogenic dose not induce overt toxicity for any organs and has no in vivo genotoxicity in the lungs.

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