Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats

Q2 Medicine

Experimental and Toxicologic Pathology Pub Date : 2017-04-04 DOI:10.1016/j.etp.2017.01.002

Sawako Kasamoto , Shoji Masumori , Jin Tanaka , Maya Ueda , Masahito Fukumuro , Miho Nagai , Jyoji Yamate , Makoto Hayashi

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引用次数: 5

Abstract

According to the International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (ICH S2(R1)), a positive response in any in vitro assay necessitates additional in vivo test(s) (other tissue/endpoint) in addition to the erythrocyte micronucleus test when Option 1 of the test battery is selected. When Option 2 of the test battery is selected, a bacterial gene mutation test and two in vivo tests with different tissues/endpoint are required. The in vivo alkaline comet assay is recommended as the second in vivo test because it can detect a broad spectrum of DNA damage in any tissue and can be combined with the erythrocyte micronucleus test. Considering animal welfare, a combination assay is preferable to an individual assay. Thus, we validated the protocol for the in vivo comet-micronucleus combination assay in rats with three daily administrations and determined the dose of the positive control (ethyl methanesulfonate; EMS, 200 mg/kg/day). We also collected the negative control (vehicle) and positive control (EMS) data from the comet (liver, stomach, and kidney) and micronucleus (bone marrow) combination assay using male Sprague Dawley (SD) rats. The negative control data were comparable to our historical control data obtained from stand-alone assays. The positive control data showed clear and consistent positive responses in both endpoints.

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参考对照数据来自于用斯普拉格-道利大鼠进行的体内彗星-微核联合试验

根据国际协调会议《人类使用药物基因毒性测试和数据解释指南》（ICH S2（R1）），当选择试验组的选项1时，任何体外试验中的阳性反应都需要在红细胞微核试验之外进行额外的体内试验（其他组织/终点）。当选择测试组的选项2时，需要进行细菌基因突变测试和两次不同组织/终点的体内测试。体内碱性彗星试验被推荐为第二种体内试验，因为它可以检测任何组织中的广谱DNA损伤，并且可以与红细胞微核试验相结合。考虑到动物福利，组合测定比单独测定更可取。因此，我们验证了每天三次给药的大鼠体内彗星微核联合测定方案，并确定了阳性对照（甲磺酸乙酯；EMS，200mg/kg/天）的剂量。我们还收集了使用雄性Sprague-Dawley（SD）大鼠进行的彗星（肝、胃和肾）和微核（骨髓）联合测定的阴性对照（载体）和阳性对照（EMS）数据。阴性对照数据与我们从独立测定中获得的历史对照数据相当。阳性对照数据在两个终点均显示出明确且一致的阳性反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental and Toxicologic Pathology 医学-病理学

CiteScore

2.08

自引率

0.00%

发文量

审稿时长

5.3 weeks

期刊介绍： Cessation. The international multidisciplinary journal is devoted to the publication of studies covering the whole range of experimental research on disease processes and toxicology including cell biological investigations. Its aim is to support progress in the interdisciplinary cooperation of researchers working in pathobiology, toxicology, and cell biology independent of the methods applied. During the past decades increasing attention has been paid to the importance of toxic influence in the pathogenesis of human and animal diseases. This is why Experimental and Toxicologic Pathology meets the urgent need for an interdisciplinary journal felt by a wide variety of experts in medicine and biology, including pathologists, toxicologists, biologists, physicians, veterinary surgeons, pharmacists, and pharmacologists working in academic, industrial or clinical institutions.