Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
J Toxicol Sci. 2012;37(4):711-21. doi: 10.2131/jts.37.711.
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.
1- 甲基萘（1-MN）是多环芳烃（PAHs）的一种成分，是小鼠肺部的致癌物质。然而，常规的遗传毒性测试，如艾姆斯测试和姐妹染色单体交换（SCE）测试，得到的结果并不明确。在本研究中，使用 B6C3F1 gpt delta 小鼠进行了为期 13 周的重复剂量毒性研究，研究了 1-MN 的体内遗传毒性及其毒理学特征。在血清生化方面，0.15% 1-MN 组雄性小鼠的 AST 和 ALP 显著升高。从组织病理学检查来看，0.15% 1-MN 组雄性小鼠肝脏单个细胞坏死的发生率显著增加；然而，1-MN 的靶器官肺部没有观察到变化。在体内突变试验中，在 13 周时，1-MN 处理小鼠肺 DNA 中的 gpt 和 red/gam（Spi-）突变频率没有变化。此外，各组雄性小鼠的细支气管上皮细胞增殖细胞核抗原（PCNA）阳性率没有显著差异。这些结果表明，在致癌剂量下，1-MN 不会引起任何器官的明显毒性，也不会在肺部引起体内遗传毒性。
