Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, MUT-2881.5.38, Basel, Switzerland.
Mutat Res. 2010 Oct 29;702(2):157-62. doi: 10.1016/j.mrgentox.2010.03.011. Epub 2010 Mar 23.
The following reference genotoxic agents were tested in the in vitro micronucleus test, at Novartis, Basel, Switzerland. Mitomycin C, 5-fluoruracil, colchicine and etoposide were tested in the human lymphoblastoid cell line TK6, with and without cytokinesis block (in the presence of cytochalasin B). This was done in support of the toxicity measures recommended in the draft OECD Test Guideline on In Vitro Mammalian Cell Micronucleus Test (MNvit) and was part of an international collaborative work. As toxicity measures, detecting cytostasis and cell death, relative cell counts (RCC), relative increase in cell counts (RICC), and relative population doubling (RPD) were used for treatments in the absence of cytokinesis block, and replication index (RI) or cytokinesis-blocked proliferation in the presence of cytokinesis block. All four reference agents were positive in the assay with and without cytokinesis block at concentrations giving approximately 50% toxicity or less as assessed by all of the toxicity measures used. Accordingly, the results of this work support the use of relative population doubling and relative increase in cell counts, as well as relative cell counts, as appropriate measures of toxicity for the non-cytokinesis-blocked in vitro micronucleus assay.
以下遗传毒性试剂在瑞士巴塞尔诺华公司的体外微核试验中进行了测试。丝裂霉素 C、5-氟尿嘧啶、秋水仙碱和依托泊苷在人淋巴母细胞系 TK6 中进行了测试,同时测试了有丝分裂细胞阻断(细胞松弛素 B 存在下)和无有丝分裂细胞阻断。这是为了支持 OECD 体外哺乳动物细胞微核试验(MNvit)毒性措施草案中的建议,并作为国际合作的一部分。作为毒性措施,用于无有丝分裂细胞阻断的处理的检测有细胞停滞和细胞死亡、相对细胞计数(RCC)、细胞计数的相对增加(RICC)和相对群体倍增(RPD),以及有丝分裂细胞阻断的复制指数(RI)或有丝分裂细胞阻断增殖。所有四种参考试剂在有丝分裂细胞阻断和无有丝分裂细胞阻断的情况下均呈阳性,浓度约为 50%或更低,如所有使用的毒性措施评估的那样。因此,这项工作的结果支持将相对群体倍增和细胞计数的相对增加以及相对细胞计数用作无有丝分裂细胞阻断体外微核试验的适当毒性措施。