Sickles D W, Welter D A, Friedman M A
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000.
J Toxicol Environ Health. 1995 Jan;44(1):73-86. doi: 10.1080/15287399509531944.
Cultured HT 1080 fibrosarcoma cells were exposed to acrylamide (ACR), an industrial neurotoxicant that disrupts neuronal intracellular transport, to determine if mitosis (another microtubule-based intracellular transport system) was adversely affected. The number of cells arrested in mitosis increased, in a concentration-dependent manner, from 1 to 10 mM acrylamide. A 4-h exposure to 10 mM acrylamide increased the mitotic index by 4.5-fold over control, comparable to the arrest caused by colchicine. In mitotic acrylamide-exposed cells, the chromosomes remained at the metaphase plate; no changes in spindle microtubules (MTs), as seen with tubulin immunofluorescence, were observed. The distance between spindle poles (interaster) was the same in control and experimental cells. The non-neurotoxic analogue methylene bisacrylamide had no effect in the same concentration range. The data suggest potential molecular mechanisms of action for general toxicity and neurotoxicity to be disruption in MT disassembly or MT-kinetochore interactions and/or cellular homeostasis.
将培养的HT 1080纤维肉瘤细胞暴露于丙烯酰胺（ACR）中，丙烯酰胺是一种工业神经毒素，可破坏神经元细胞内运输，以确定有丝分裂（另一种基于微管的细胞内运输系统）是否受到不利影响。在1至10 mM丙烯酰胺浓度范围内，停滞在有丝分裂期的细胞数量呈浓度依赖性增加。暴露于10 mM丙烯酰胺4小时，有丝分裂指数比对照增加了4.5倍，与秋水仙碱引起的停滞相当。在暴露于丙烯酰胺的有丝分裂细胞中，染色体停留在中期板；用微管蛋白免疫荧光观察，纺锤体微管（MTs）没有变化。对照细胞和实验细胞中纺锤体极之间的距离（星体间距离）相同。非神经毒性类似物亚甲基双丙烯酰胺在相同浓度范围内没有作用。数据表明，一般毒性和神经毒性的潜在分子作用机制是微管拆卸或微管-动粒相互作用和/或细胞内稳态受到破坏。
