Abstract
Until now, kinetic perturbations induced by cytotoxic drugs during the therapy of leukemia have mainly been investigated by measuring changes in the proportion of cells in mitosis (mitotic index=IM) and/or in DNA-synthesis phase (tritiated thymidine labeling index=IL). This study was designed to determine simultaneously the effect of arabinosyl cytosine (ARA-C) on the IM, the IL, and also the flux of the cells through mitosis. For that purpose, the rate of accumulation of the cells in mitosis following vincristine was measured in vivo before and after a 3-day course of ARA-C in 2 patients with Ph 1 positive chronic myeloid leukemia. It was found that ARA-C increased the IL, as expected, but also the IM of granulocytic precursors, which could not have been predicted. The increased IM was due to prolonged mitosis, whereas the cell flux through mitosis (=cell birth rate) was actually reduced. The data show that cell flux studies are needed for appropriate estimation of cell kinetic effects of cytotoxic drugs and that reliance on cell cycle ‘indices’ alone in some instances may be misleading.
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