Valeriote F A, Bruce W R, Meeker B E
Biophys J. 1966 Mar;6(2):145-52. doi: 10.1016/S0006-3495(66)86646-8.
A model for the action of vinblastine (VLB) on cells multiplying exponentially in vivo with a generation time, T(G), has been derived. It is based on the assumption that cells attempting to pass through mitosis in the presence of VLB lose their proliferative capacity and that this lethal effect occurs only when the cells are exposed to a concentration of VLB which is above a critical value, C(k). The model leads to two predictions. First, that the percentage of cells surviving at any time after exposure to a dose, D, of VLB is 100% if D < D(k) and decreases to 0% after a time, T(G), following a dose D >/= D(k).2(T G/T1/2), where D(k) represents the dose of VLB required to produce the concentration C(k), and T(1/2) is the half-life of the VLB in vivo. Second, that the time, T(G), at which the percentage of cells surviving an exposure to VLB, at doses greater than D(k).2(U G/T1/2), decreases to zero should be equal to the generation time of the cells. Both of these predictions were confirmed experimentally which indicates that the model adequately explains the action of VLB in vivo.
已推导了一个关于长春碱（VLB）对体内以代时T（G）呈指数增殖的细胞的作用模型。该模型基于这样的假设：在有VLB存在的情况下试图通过有丝分裂的细胞会丧失其增殖能力，且这种致死效应仅在细胞暴露于高于临界值C（k）的VLB浓度时才会发生。该模型得出两个预测。其一，暴露于剂量D的VLB后，若D < D（k），则在任何时间存活细胞的百分比为100%；若剂量D≥D（k）·2（T G/T1/2），则在经过时间T（G）后存活细胞百分比降至0%，其中D（k）表示产生浓度C（k）所需的VLB剂量，T（1/2）是VLB在体内的半衰期。其二，暴露于大于D（k）·2（T G/T1/2）剂量的VLB后，存活细胞百分比降至零的时间T（G）应等于细胞的代时。这两个预测均得到了实验证实，这表明该模型充分解释了VLB在体内的作用。
