Martin M L, Regan C M
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Brain Res. 1991 Jul 19;554(1-2):223-8. doi: 10.1016/0006-8993(91)90193-y.
Direct cell counting and extent of [3H]thymidine incorporation demonstrated valproate to inhibit C6 glioma proliferation rate in a dose-dependent manner with a 1 mM concentration achieving 50% inhibition. The antiproliferative effect was reversible and could not be attributed to cytotoxicity at the valproate concentrations employed. The site of valproate action within the cell cycle was determined to be in the G1 phase, at a point 6-6.5 h prior to S phase, by estimating the time to increased [3H]thymidine incorporation following release from a 70% proliferative arrest. Synchronised cells obtained by a mitotic selection procedure required 11-12 h to enter S phase and demonstrated the valproate restriction point to be 5 h into the G1 phase of the C6 cell cycle. Exposure of valproate to the part of the G1 period which follows the restriction point was without effect on cell entry into S phase.
直接细胞计数和[3H]胸苷掺入程度表明，丙戊酸盐以剂量依赖方式抑制C6胶质瘤的增殖率，1 mM浓度可实现50%的抑制。这种抗增殖作用是可逆的，在所使用的丙戊酸盐浓度下，不能归因于细胞毒性。通过估计从70%增殖停滞释放后[3H]胸苷掺入增加的时间，确定丙戊酸盐在细胞周期内的作用位点是在G1期，在S期前6 - 6.5小时。通过有丝分裂选择程序获得的同步化细胞需要11 - 12小时进入S期，并证明丙戊酸盐限制点位于C6细胞周期G1期的5小时。将丙戊酸盐暴露于限制点之后的G1期部分对细胞进入S期没有影响。
