Masuda Akane, Masuda Miyabi, Kawano Takuya, Kitsunai Yoko, Nakayama Haruka, Nakajima Hiroyuki, Kojima Hiroyuki, Kitamura Shigeyuki, Uramaru Naoto, Hosaka Takuomi, Sasaki Takamitsu, Yoshinari Kouichi
Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka.
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University.
Yakugaku Zasshi. 2017;137(5):611-622. doi: 10.1248/yakushi.16-00259.
Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.
接触化学物质可诱导肝脏和肝细胞肥大，但这些现象的机制和毒理学特征尚未得到广泛研究。特别是，由化学物质诱导的肝细胞肥大应被判定为适应性反应还是不良反应仍不清楚。因此，了解肝细胞肥大的毒理学特征对于农药和其他化学物质的安全性评价至关重要。为此，我们构建了一个潜在有毒农药数据库。利用日本食品安全委员会公开提供的农药风险评估报告，我们提取了所有基于大鼠90天亚急性毒性试验以及2年慢性毒性和致癌性试验的观察结果/发现。对该数据库的分析表明，在所研究的农药中，37%-47%观察到肝细胞肥大（因性别和试验周期而异），并且在90天和2年的研究中，小叶中央肝细胞肥大在各种类型的肝细胞肥大中最为常见。本研究构建的数据库使我们能够研究肝细胞肥大与其他毒理学观察结果/发现之间的关系，因此将有助于表征肝细胞肥大。
