Covance Laboratories Ltd., Harrogate, UK.
Mutat Res. 2010 Oct 29;702(2):175-80. doi: 10.1016/j.mrgentox.2010.02.018. Epub 2010 Mar 10.
The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the Chinese hamster lung cell line CHL. Etoposide (a topoisomerase inhibitor), colchicine (an aneugen), mitomycin C (a DNA cross linking agent) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay.
以下致突变化学物质在英国哈罗盖特的 Covance 实验室的中国仓鼠肺细胞系 CHL 中进行了体外微核试验,分别是依托泊苷(拓扑异构酶抑制剂)、秋水仙碱(着丝粒毒物)、丝裂霉素 C(DNA 交联剂)和环磷酰胺(需要代谢激活的烷化剂)。这些药物与细胞分裂阻断(加入细胞松弛素 B)一起或不一起进行处理。这项工作是对 OECD 草案测试指南 487 中体外微核试验推荐的毒性测量进行的合作评估的一部分。所使用的毒性测量方法,既检测细胞抑制又检测细胞死亡,包括相对群体倍增、细胞计数的相对增加和无细胞分裂阻断处理的相对细胞计数,以及有细胞分裂阻断时的复制指数或细胞分裂阻断增殖指数。所有测试的化学物质在有和没有细胞分裂阻断的情况下,在导致大约 60%毒性(细胞抑制和细胞死亡)或更低的浓度下,均导致微核细胞百分比显著增加,所有使用的毒性测量方法都得出了这一结果。这一系列测试的结果支持将细胞计数的相对增加、群体倍增的相对增加以及适当的细胞计数,作为非细胞分裂阻断体外微核试验的细胞毒性的适当测量方法。