Oguro M, Takagi T, Takenaga K
Jpn J Cancer Res. 1985 Feb;76(2):131-41.
Continuous observation of living malignant cells (L1210) in a specially devised glass observation chamber with an inverted microscope made it possible to classify various cellular morphological features induced by antitumor agents into the following four stages: 1) an initial stage consisting of cytoplasmic granulation and coloring, 2) an intermediate stage of shrinkage of nuclei, increases of vacuoles and cytoplasmic budding, 3) a determinate stage of cell ballooning and 4) the terminal stage (cell ghost). Both the initial and intermediate stages are characterized by cellular changes that appear at an early phase and remain opportunistic in terms of viability. Emergence of these cellular changes is largely dependent on the specific mode of action of antitumor agents. In contrast, definite irreversibility in the changes found in both the terminal and determinate stages was confirmed by continuous observation until the cells showed lytic or ghost features, using a video-recording system. A plot of the number of cells counted in both the determinate and terminal stages versus the time-dose schedule is designated as the "time-dose-response" plot, and this proved useful for estimating the characteristics of the antitumor agents tested and the actions of new antitumor agents on malignant cells (predictive activity assay graph).
在一个特别设计的玻璃观察室中，使用倒置显微镜对活的恶性细胞（L1210）进行连续观察，使得将抗肿瘤药物诱导的各种细胞形态特征分为以下四个阶段成为可能：1）由细胞质颗粒化和染色组成的初始阶段；2）细胞核收缩、液泡增加和细胞质出芽的中间阶段；3）细胞膨胀的确定阶段；4）终末阶段（细胞残影）。初始阶段和中间阶段的特征都是在早期出现的细胞变化，并且在活力方面仍然具有不确定性。这些细胞变化的出现很大程度上取决于抗肿瘤药物的特定作用方式。相比之下，通过使用视频记录系统持续观察直至细胞呈现溶解或残影特征，证实了终末阶段和确定阶段所发现的变化具有明确的不可逆性。将确定阶段和终末阶段计数的细胞数量与时间-剂量方案绘制的图称为“时间-剂量-反应”图，这被证明对于评估所测试的抗肿瘤药物的特征以及新抗肿瘤药物对恶性细胞的作用（预测活性测定图）很有用。
