A comparison of two in vitro mammalian cell cytogenetic assays for the detection of mitotic aneuploidy using 10 known or suspected aneugens.
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.
Warr
T J
TJ
School of Biological Sciences, University College of Swansea, UK.
Parry
E M
EM
Parry
J M
JM
D000782:Aneuploidy; D000818:Animals; D002104:Cadmium / Q000633:toxicity; D019256:Cadmium Chloride; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002503:Centromere / Q000187:drug effects*; D002697:Chloral Hydrate / Q000633:toxicity; D002712:Chlorides / Q000633:toxicity; D003078:Colchicine / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D003975:Diazepam / Q000633:toxicity; D004464:Econazole / Q000633:toxicity; D006873:Hydroquinones / Q000633:toxicity; D007621:Karyotyping; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D011739:Pyrimethamine / Q000633:toxicity; D013827:Thiabendazole / Q000633:toxicity; D013849:Thimerosal / Q000633:toxicity; D014747:Vinblastine / Q000633:toxicity
D002712:Chlorides; D006873:Hydroquinones; D009153:Mutagens; D002104:Cadmium; D013849:Thimerosal; D002697:Chloral Hydrate; D014747:Vinblastine; D004464:Econazole; D019256:Cadmium Chloride; D013827:Thiabendazole; D003975:Diazepam; D003078:Colchicine; C031927:hydroquinone; D011739:Pyrimethamine