Chang W W, Mak K M, Macdonald P D
Virchows Arch B Cell Pathol Incl Mol Pathol. 1979 Jun 29;30(3):349-61. doi: 10.1007/BF02889113.
The parameters of cell population kinetics of symmetrical 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse were analyzed using the fraction labeled-mitoses curve method and compared with those of three groups of epithelial cells in the crypt of the descending colon of normal mouse. The analysis of three groups of epithelial cells in the crypt of normal mouse indicates that differentiation of epithelial cells was associated not only with a smaller proliferative pool of cells but also with a shortening of the duration of G2 phase and a prolongation of mitotic time. Other parameters of cell cycle did not change significantly. The mean cell cycle time of neoplastic cells in chemically induced colonic neoplasms was similar to that of epithelial cells in normal colon, but the variance was much greater in neoplastic cells. In neoplastic cells, the proliferative pool was greater, the G1 phase prlonged, and the S phase and the mitotic time became shorter as compared to epithelial cells in normal colon. The duration of G2 phase of neoplastic cells fell between the values of presumptive stem cells and differentiating cells in normal colon, compatible with the hypothesis that neoplastic cells are transformed stem cells defective in cellular differentiation. In the colonic mucosa immediately adjacent to neoplasms, the fraction-labeled-mitoses curve showed a flat second wave, indicating that the group of cells initially labeled by the pulse became a mixture of cells, some continuing the proliferative cycle normally, some going out of cycle, some slowing down in their passage from S through G2 to M, and some being arrested in mitotic phase. Such heterogeneous behavior of cells may be closely related to expansion of neoplasms. With some assumptions, however, cell cycle parameters of those normally cycling cells were estimated: the cell cycle time and the duration of G1 phase and mitotic phase were prolonged as compared to neoplastic cells and epithelial cells of normal colon.
采用标记有丝分裂分数曲线法分析了对称1,2 - 二甲基肼诱导的小鼠结肠肿瘤及其相邻结肠黏膜的细胞群体动力学参数，并与正常小鼠降结肠隐窝中三组上皮细胞的参数进行了比较。对正常小鼠隐窝中三组上皮细胞的分析表明，上皮细胞的分化不仅与较小的增殖细胞池有关，还与G2期持续时间缩短和有丝分裂时间延长有关。细胞周期的其他参数没有显著变化。化学诱导的结肠肿瘤中肿瘤细胞的平均细胞周期时间与正常结肠上皮细胞相似，但肿瘤细胞的方差要大得多。与正常结肠上皮细胞相比，肿瘤细胞的增殖池更大，G1期延长，S期和有丝分裂时间变短。肿瘤细胞的G2期持续时间介于正常结肠假定干细胞和分化细胞的值之间，这与肿瘤细胞是细胞分化有缺陷的转化干细胞这一假设相符。在紧邻肿瘤的结肠黏膜中，标记有丝分裂分数曲线显示出一个平坦的第二波，表明最初被脉冲标记的细胞群体变成了一个混合细胞群体，一些细胞正常继续增殖周期，一些细胞退出周期，一些细胞从S期到G2期再到M期的进程减慢，一些细胞停滞在有丝分裂期。细胞的这种异质性行为可能与肿瘤的扩展密切相关。然而，在一些假设的基础上，估计了那些正常循环细胞的细胞周期参数：与肿瘤细胞和正常结肠上皮细胞相比，细胞周期时间以及G1期和有丝分裂期的持续时间延长。
