BACKGROUND & AIMS:
:Since there are no systematic studies available on the effects of anti-microtubule agents on ciliated protozoa, we screened a wide variety of such compounds for their effects on the growth of Paramecium tetraurelia cell cultures. Compounds tested include agents of widely different chemical composition and with reported effects on widely different cell types. We can differentiate between different drug effects: (a) Rotenone is the only agent without any recognisable effect, (b) Another group of compounds (including colchicine) requires very high concentrations, as compared to higher animal cells, i.e., rather close to a cytotoxic level; this group also includes tubulozole (unexpectedly without any difference between the cis- and the trans-stereoisomer). (c) A third group of drugs inhibits cell culture growth without any lethal effects (benzimidazoles, nocodazole, parbendazole; the [anti-]fungal antibiotic, griseofulvin; the herbicide, trifluralin). (d) Finally a group of agents are active in a concentration range also reported for plants (the herbicide, APM) or for higher animal cells (including the microtubule stabiliser, taxol) or for both (vinblastine, vincristine, triethyl lead), although they are cytotoxic at higher concentrations (like compounds of group [b]). Therefore, in particular compounds of group (c) and possibly of group (d) might be considered further on for a more detailed analysis of a possibly genuine anti-microtubular effect in Paramecium cells. Of particular interest may be nocodazole, parbendazole and trifluralin, since they can inhibit cell culture growth (over 24 h tested) in relatively low concentrations (comparable to other cell types) without any impairment of cell viability.
背景与目标:
:由于尚无关于抗微管剂对纤毛虫原虫影响的系统研究,因此我们筛选了多种此类化合物对草履虫草履虫细胞培养物生长的影响。测试的化合物包括化学成分差异很大的试剂,并且据报道对多种细胞类型具有影响。我们可以区分不同的药物作用:(a)鱼藤酮是唯一没有任何可识别作用的药物,(b)与较高的动物细胞相比,另一组化合物(包括秋水仙碱)需要很高的浓度,即接近细胞毒性水平;该组还包括微管唑(出乎意料的是,顺式和反式立体异构体之间没有任何区别)。 (c)第三类药物抑制细胞培养物的生长而没有任何致死作用(苯并咪唑,诺考达唑,苯达达唑; [抗]真菌抗生素,灰黄霉素;除草剂三氟拉林)。 (d)最后,一组试剂在植物(除草剂,APM)或高级动物细胞(包括微管稳定剂,紫杉醇)或两者(长春碱,长春新碱,三乙基铅)的浓度范围内均具有活性。它们在较高浓度下具有细胞毒性(如[b]组化合物)。因此,对于草履虫细胞中可能真正的抗微管作用的更详细的分析,可以进一步考虑组(c)以及可能的组(d)的化合物。 Nocodazole,parbendazole和trifluralin特别令人感兴趣,因为它们可以在相对低的浓度下(与其他细胞类型相比)抑制细胞培养物的生长(经过24小时测试),而不会损害细胞的活力。