Toffoli G, Viel A, Bevilacqua C, Maestro R, Tumiotto L, Boiocchi M
Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
Leuk Res. 1989;13(4):279-87. doi: 10.1016/0145-2126(89)90064-7.
The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.
在诱导分化的白血病细胞系中，c-myc mRNA表达的降低被认为是启动分化程序的早期事件。或者，c-myc mRNA表达的降低可能仅仅是终末分化表型所特有的自我更新能力丧失的结果。为了阐明这些假设，我们比较分析了正常和经血红素处理的K562白血病细胞在不同时间段暴露于抗肿瘤抗生素阿霉素后，c-myc mRNA表达、血红蛋白合成、DNA和RNA合成、细胞周期动力学以及自我更新能力的变化动力学。阿霉素的暴露时间为2小时，这导致血红蛋白合成的可逆诱导且无明显的细胞生长抑制作用，或者连续暴露超过5天，这导致血红蛋白合成的不可逆诱导以及自我更新活性的完全且不可逆丧失。对实验数据的比较分析表明，c-myc mRNA表达的降低与复制活性的丧失相关，这可能是由于长时间暴露于阿霉素产生的不可逆细胞生长抑制作用，但与分化程序的启动无关。
