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Colchicine causes prenatal cell toxicity and increases tetraploid risk
BMC Pharmacology and Toxicology ( IF 2.8 ) Pub Date : 2019-11-13 , DOI: 10.1186/s40360-019-0365-z
Ding Wang , Yingjun Xie , Minyi Yan , Qianying Pan , Yi Liang , Xiaofang Sun

Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

中文翻译:

秋水仙碱引起产前细胞毒性并增加四倍体风险

秋水仙碱是用于缓解痛风和家族性地中海热的临床药物。由于其毒性作用,已禁止静脉注射秋水仙碱,但仍广泛口服。我们测定了秋水仙碱在培养的绒毛膜绒毛细胞和羊水细胞中的毒性作用,以解释其对胎盘和胎儿的影响。明场记录和细胞计数试剂盒8用于评估细胞活力。流式细胞仪用于鉴定细胞标志物,细胞周期和细胞凋亡。G谱带用于核型分析,用于样品遗传和药物作用评估。绒毛膜绒毛细胞和羊水细胞的特征是间充质细胞,它们共享大多数细胞表面标记,并对秋水仙碱具有相似的反应。秋水仙碱在低浓度下不会引起细胞活力的下降,但在小部分病例中通过将细胞周期停滞在G2 / M期而抑制了细胞增殖,并增加了产生四倍体的风险。我们的研究揭示了秋水仙碱诱导的产前细胞毒性试验的结果,并确定了可降低四倍体生成风险的抗有丝分裂生物学功能剂量和给药方式。
更新日期:2020-04-22
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