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首页> 外文期刊>The Journal of toxicological sciences >Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test
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Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test

机译：成年小鼠重复剂量肝微核试验与多种基因毒性试验同时进行，作为联合试验

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Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N, N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days. Then, the liver MN assay, peripheral blood (PB) MN assay and comet assay using the liver and kidney were concurrently performed as a combination test. DEN showed positive responses to all endpoints except MN induction in PB after 15 days of repeat administration. A cross-linking agent, CIS, showed MN induction in liver after 29 days of repeat administration, and in PB after 15 and 29 days of repeat administration, although the comet assay yielded negative responses for both organs at both sampling times. PHE yielded negative responses for all endpoints. In conclusion, it is suggested that the RDLMN assay using mice is a feasible method to be integrated into the general repeated toxicity test along with the combination assays, i.e., comet assay or PB MN assay, which would help in risk assessment for carcinogenicity by comparing the results of combination assays with each other.
机译：最近，Narumi等人采用不进行部分肝切除术或原位胶原酶灌注的新方法作为重复剂量肝MN（RDLMN）测定方法，对使用年轻成年大鼠重复给药的肝微核（MN）测定方法进行了研究。 （2012）。在我们的研究中，为了研究使用成年小鼠而非大鼠进行RDLMN分析的可能性以及将某些遗传毒性分析与RDLMN分析作为组合测试的可行性，两种遗传毒性致癌物（N，N-二乙基亚硝胺（DEN） ）和顺铂（CIS））和非遗传毒性致癌物（苯巴比妥钠（PHE））给予小鼠15或29天。然后，同时进行使用肝脏和肾脏的肝脏MN测定，外周血（PB）MN测定和彗星测定作为组合测试。重复给药15天后，DEN对所有终点均显示阳性反应，但PB中的MN诱导除外。交联剂CIS在重复给药29天后在肝脏中显示出MN诱导，在重复给药15和29天后在PB中显示出MN诱导，尽管彗星试验在两个采样时间均对两个器官产生了阴性反应。 PHE对所有终点均产生阴性反应。总之，建议使用小鼠的RDLMN测定法是一种可行的方法，该方法可与常规测定法（彗星测定法或PB MN测定法）等组合测定法结合到常规重复毒性试验中，这将有助于通过比较来评估致癌性的风险。相互结合测定的结果。

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