Resonance effect in self-renewing tissues
Resonance effect in self-renewing tissues
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DOI：
10.1006/jtbi.1997.0613
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发表时间：
1998-05-07
影响因子：
2
通讯作者：
Dibrov, BF
中科院分区：
文献类型：
--
作者：
Dibrov, BF
先前预测，细胞群体的耗竭极大地依赖于细胞的周期性阶段特异性杀伤的周期，并且在接近平均细胞周期时间的整数倍的周期，处理诱导的细胞群体大小的减少显著减少（共振效应）。本文从理论和实验两个方面对自我更新组织中的共振效应进行了研究。主要的生物学假设的共振效应的想法进行了讨论，然后重新制定的数学模型。该模型描述了高剂量的具有阻断作用的阶段特异性细胞毒性剂定期治疗下的细胞群体的动力学。本文研究了细胞周期参数和处理参数对细胞存活率的影响，并给出了适合于实验检验和实际应用的结果，为利用共振效应进行自我更新的组织对照研究和估计各种细胞（包括形态学上无法识别的细胞）的细胞周期参数提供了理论依据。对小鼠脾集落形成单位（CFUs）、小鼠小肠上皮细胞和L1210白血病细胞的实验数据进行了定量比较，证明了理论与实验结果的良好一致性，并对小鼠小肠上皮细胞的CFUs、隐源性细胞和转运细胞的周期参数进行了估计。生物学后果所获得的结果进行了讨论，并提出了新的假设相对于自我更新的组织增殖控制。(C)出版社：Academic Press Limited。
It was predicted previously that a depletion of cell population depends extremely on the period of periodic phase-specific killing of cells and at periods near the integer multiple of the mean cell-cycle time there is a considerable reduction in treatment-induced decrease of cell-population size (resonance effect). This paper is devoted to theoretical and experimental analysis of the resonance effect in self-renewing tissues. The main biological assumptions underlying the idea of the resonance effect are discussed and then reformulated in terms of a mathematical model. The model describes kinetics of cell populations under periodic treatment by high doses of a phase-specific cytotoxic agent with blocking effect. The dependence of cell survival on cell-cycle parameters and parameters of treatment is studied and the results are presented in a suitable form for experimental testing and practical usage.The obtained results give a theoretical basis for using the resonance effect in a self-renewing tissue control study and estimation of cell-cycle parameters of various cells including morphologically unrecognizable ones. The quantitative comparison of the theoretical predictions with experimental data obtained for mice spleen colony forming units (CFUs), cells of mice small intestine epithelium as well L1210 leukemic cells is carried out.The excellent agreement between theoretical and experimental results is demonstrated and the estimations of cycle parameters of CFUs, cryptogenic and transit cells of mice intestine epithelium are obtained. Biological consequences of the obtained results are discussed and the new hypothesis relative to self-renewing tissue proliferative control is put forward. (C) 1998 Academic Press Limited.