Glinos A D, Bardi G N, Dermitzaki K C, Perez S A, Talieri M J
J Natl Cancer Inst. 1983 Dec;71(6):1211-9.
Total and viable cell counts, differential mitotic cell counts, and incorporation of tritiated thymidine were used to study the kinetics of suspension cultures of HeLa cells exposed to urea concentrations of 0.5-1.5%. Aside from any nonspecific osmotic effects, urea concentrations of 1.0-1.4% exhibited significant cytokinetic and cytotoxic effects. Most characteristically, mitotic cells arrested in metaphase began to accumulate 4-6 hours after addition of urea and reached a peak at 15-18 hours. Thus when the cells were in the S-phase or at the S/G2 boundary at the time of addition of urea, they exhibited metaphase arrest. Subsequently, cultures continuously exposed to urea showed a decline in the mitotic index, indicating that the entry rate of cells into mitosis is lower than the rate at which cells escape from the mitotic block. Such cultures exhibited numerous abnormal and abortive mitoses and a decrease in growth and viability of the cell populations. In contrast to the initial single wave of arrested mitosis seen with continuous exposure to urea, intermittent exposure on alternate days resulted in successive waves of arrested metaphases and had considerably more pronounced effects on the growth and viability of the cultures.
通过总细胞计数和活细胞计数、有丝分裂细胞差异计数以及氚标记胸腺嘧啶核苷掺入量，研究了暴露于0.5 - 1.5%尿素浓度下的HeLa细胞悬浮培养物的动力学。除了任何非特异性渗透效应外，1.0 - 1.4%的尿素浓度表现出显著的细胞动力学和细胞毒性效应。最典型的是，添加尿素后4 - 6小时，停滞在中期的有丝分裂细胞开始积累，并在15 - 18小时达到峰值。因此，当在添加尿素时细胞处于S期或S/G2边界时，它们会出现中期停滞。随后，持续暴露于尿素的培养物有丝分裂指数下降，表明细胞进入有丝分裂的速率低于细胞从有丝分裂阻滞中逃脱的速率。此类培养物表现出大量异常和夭折的有丝分裂，以及细胞群体生长和活力的下降。与持续暴露于尿素时最初出现的单一波有丝分裂停滞不同，隔天间歇性暴露会导致连续的中期停滞波，并且对培养物的生长和活力有更明显的影响。
