Warr T J, Parry E M, Parry J M
School of Biological Sciences, University College of Swansea, UK.
Mutat Res. 1993 May;287(1):29-46. doi: 10.1016/0027-5107(93)90143-4.
Two in vitro cytogenetic assays were evaluated for their ability to detect aneugenic and polyploidy-inducing agents using a battery of 10 known or suspected aneugens supplied as part of the EEC 4th Environmental Research and Development Programme. The compounds tested were colchicine, vinblastine, chloral hydrate, thiabendazole, hydroquinone, thimerosal, cadmium chloride, econazole nitrate, pyrimethamine and diazepam. The cell division aberration assay employed a differential chromosome/spindle staining procedure to detect perturbations of the mitotic division apparatus. This assay was carried out in two pulmonary-derived Chinese hamster cell lines; the immortal DON:Wg3h culture and a low passage LUC2 culture. The second assay involved quantification of metaphase chromosomes, for which only the LUC2 cell line was used, due to the stability of its diploid karyotype. All the chemicals induced spindle disturbances in the immortal line. In addition, all the compounds except cadmium chloride yielded positive results in the LUC2 culture, although many were not as potent. In the low passage line, 8 of the compounds (colchicine, vinblastine, chloral hydrate, thiabendazole, thimerosal, econazole nitrate, pyrimethamine and diazepam) induced aneuploidy and/or tetraploidy. Cadmium chloride was negative in the chromosome enumeration assay and hydroquinone yielded inconclusive results. The study of cell division aberrations was much less time-consuming and technically complex than the counting of metaphase chromosomes. In addition, it provided a degree of mechanistic understanding of the mode of action of some aneugenic and polyploidy-producing agents. However, the enumeration of chromosomes provides a more definitive data set for the evaluation of a chemical's aneugenic potential.
利用作为欧洲经济共同体第4个环境研究与发展计划一部分提供的一组10种已知或疑似非整倍体诱导剂，对两种体外细胞遗传学检测方法检测非整倍体诱导剂和多倍体诱导剂的能力进行了评估。所测试的化合物有秋水仙碱、长春碱、水合氯醛、噻苯达唑、对苯二酚、硫柳汞、氯化镉、硝酸益康唑、乙胺嘧啶和地西泮。细胞分裂畸变检测采用了一种差异染色体/纺锤体染色程序来检测有丝分裂装置的扰动。该检测在两种源自肺的中国仓鼠细胞系中进行；永生的DON:Wg3h培养物和低传代的LUC2培养物。第二种检测涉及中期染色体的定量分析，由于其二倍体核型的稳定性，仅使用了LUC2细胞系。所有化学物质在永生细胞系中均诱导了纺锤体紊乱。此外，除氯化镉外，所有化合物在LUC2培养物中均产生了阳性结果，尽管许多化合物的效力不如其他化合物。在低传代细胞系中，8种化合物（秋水仙碱、长春碱、水合氯醛、噻苯达唑、硫柳汞、硝酸益康唑、乙胺嘧啶和地西泮）诱导了非整倍体和/或四倍体。氯化镉在染色体计数检测中呈阴性，对苯二酚产生了不确定的结果。细胞分裂畸变的研究比中期染色体计数耗时少得多，技术上也不那么复杂。此外，它对一些非整倍体诱导剂和多倍体产生剂的作用模式提供了一定程度的机制理解。然而，染色体计数为评估化学物质的非整倍体诱导潜力提供了更明确的数据集。
