Albertini S, Brunner M, Würgler F E
Department of Toxicology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Environ Mol Mutagen. 1993;21(2):180-92. doi: 10.1002/em.2850210211.
We tested six additional chemicals (acetaldehyde, benomyl, diethylstilboestrol, diethylstilboestrol dipropionate, griseofulvin, and mercaptoethanol) for in vitro systems of the coordinated programme to study aneuploidy induction sponsored by the Commission of the European Communities in two in vitro test systems. Using Saccharomyces cerevisiae D61.M (mitotic chromosomal malsegregation assay), benomyl showed a dose-dependent increase in the frequency of chromosomal malsegregation with a lowest effective dose tested (LEDT) of 30 micrograms/ml (0.1 mM). Diethylstilboestrol (DES) showed solvent-dependent effects. DES dissolved in ethanol induced an increase in chromosomal malsegregation as well as in the frequency of total resistant colonies (mutations and recombinations) with a LEDT around 13 micrograms/ml (0.048 mM). Using dimethylsulfoxide as the solvent, no increases were observed with DES up to 333 micrograms/ml (1.24 mM). Acetaldehyde induced an increase in chromosomal malsegregation with the cold treatment protocol (LEDT: 1.25 microliters/ml (21 mM) and 0.75 microliters/ml (13 mM), respectively) but no increase with the overnight protocol (highest dose tested (HDT): 1.75 microliters/ml; 30 mM). Concerning the frequency of total cycloheximide-resistant colonies (mutations and recombinations) increases were obtained with both protocols. The other three compounds were negative when tested up to toxic doses (survival below 10%), up to the maximum solubility in the solvent used or up to heavy precipitation in the incubation mix. The HDT were 333 micrograms/ml (0.88 mM) for diethylstilboestrol dipropionate, 1,600 micrograms/ml (4.5 mM) for griseofulvin and 0.5 microliters/ml (7 mM) for mercaptoethanol. Concerning effects on porcine brain tubulin assembly in vitro, diethylstilboestrol and griseofulvin inhibited the assembly process. The IC30% (30% inhibition concentration) values were 12.5 microM and 100 microM for DES and griseofulvin, respectively. Mercaptoethanol showed no effects up to 50 mM.
我们在由欧洲共同体委员会赞助的研究非整倍体诱导的协调计划的体外系统中，在两个体外测试系统中测试了另外六种化学物质（乙醛、苯菌灵、己烯雌酚、己烯雌酚二丙酸酯、灰黄霉素和巯基乙醇）。使用酿酒酵母D61.M（有丝分裂染色体错分测定法），苯菌灵显示染色体错分频率呈剂量依赖性增加，最低有效测试剂量（LEDT）为30微克/毫升（0.1毫摩尔）。己烯雌酚（DES）显示出溶剂依赖性效应。溶解于乙醇中的DES会导致染色体错分增加以及总抗性菌落（突变和重组）频率增加，LEDT约为13微克/毫升（0.048毫摩尔）。使用二甲基亚砜作为溶剂时，高达333微克/毫升（1.24毫摩尔）的DES未观察到增加。乙醛在冷处理方案下会导致染色体错分增加（LEDT分别为1.25微升/毫升（21毫摩尔）和0.75微升/毫升（13毫摩尔）），但在过夜方案下未增加（最高测试剂量（HDT）：1.75微升/毫升；30毫摩尔）。关于总环己酰亚胺抗性菌落（突变和重组）的频率，两种方案均有增加。其他三种化合物在测试至有毒剂量（存活率低于10%）、所用溶剂中的最大溶解度或孵育混合物中出现大量沉淀时均为阴性。己烯雌酚二丙酸酯的HDT为333微克/毫升（0.88毫摩尔），灰黄霉素为1600微克/毫升（4.5毫摩尔），巯基乙醇为0.5微升/毫升（7毫摩尔）。关于对猪脑微管蛋白体外组装的影响，己烯雌酚和灰黄霉素抑制组装过程。DES和灰黄霉素的IC30%（30%抑制浓度）值分别为12.5微摩尔和100微摩尔。巯基乙醇在高达50毫摩尔时无影响。
