Waxman S, Scher W, Scher B M
Cancer Detect Prev. 1986;9(3-4):395-407.
The induction of differentiation in several tumor lines serves as a basis for a new approach to cancer treatment. In vitro studies in the mouse erythroleukemia (MEL) cell system have identified about 300 agents capable of inducing differentiation by mechanisms that remain to be elucidated. The design of differentiation therapy will depend on the specific tumor cell type, an effective time course, and the synergistic interaction among combinations of two or more inducers. The induction of differentiation may be followed by terminal cell division (TCD) or programmed cell death in several tumor cell systems. This mechanism for the destruction of tumor cells is one goal of differentiation therapy and differs from nonspecific cytotoxic therapy. To evaluate the effect of differentiation therapy, a clear distinction must be made between nonspecific cytotoxicity and the programmed TCD of induced cytodifferentiation. One possible parameter for assessing the commitment to TCD in the MEL cell system is a selective decrease in DNA ligase activity, which does not appear to occur following treatment with nonspecific cytotoxic agents. These biological and biochemical parameters should be helpful in designing agents capable of inducing TCD in vivo.
诱导多种肿瘤细胞系分化是癌症治疗新方法的基础。对小鼠红白血病（MEL）细胞系统的体外研究已鉴定出约300种能够通过尚待阐明的机制诱导分化的药物。分化疗法的设计将取决于特定的肿瘤细胞类型、有效的时间进程以及两种或更多诱导剂组合之间的协同相互作用。在几种肿瘤细胞系统中，诱导分化后可能会发生终末细胞分裂（TCD）或程序性细胞死亡。这种破坏肿瘤细胞的机制是分化疗法的一个目标，与非特异性细胞毒性疗法不同。为了评估分化疗法的效果，必须明确区分非特异性细胞毒性和诱导细胞分化后的程序性TCD。评估MEL细胞系统中TCD发生情况的一个可能参数是DNA连接酶活性的选择性降低，用非特异性细胞毒性药物处理后似乎不会出现这种情况。这些生物学和生化参数应有助于设计能够在体内诱导TCD的药物。
