Abstract
By means of flow cytometric recording of DNA histograms and counting of cells in synchronized populations, we have found that misonidazole (MIS) in clinically relevant concentrations induces cell-kinetic changes in human cells (NHIK 3025) cultivated in vitro under aerobic conditions. The effect seems to be a general lengthening of the cell cycle, affecting all phases. However, induction of this effect is phase-dependent, since only cells exposed to MIS during mitosis and/or early G1 will suffer significant cell-cycle prolongation. In exponentially growing populations this effect of MIS leads to a transient increase in the fraction of G1 cells and a corresponding decrease in the fraction of S cells. The possible significance of this effect for the clinical use of MIS is discussed.
Highlights
In exponentially growing populations this effect of MIS leads to a transient increase in the fraction of Gl cells and a corresponding decrease in the fraction of S cells
When 1mM MIS was added before selection (Panel A), the cells showed a significant cell-cycle prolongation during the first generation
The present results show that under aerobic conditions MIS induces cell-cycle inhibition in the human cell line NHIK
Summary
In exponentially growing populations this effect of MIS leads to a transient increase in the fraction of Gl cells and a corresponding decrease in the fraction of S cells. While the cytotoxic effects of MIS have been studied both in vitro (Hall & RoizinTowle, 1975; Moore et al, 1976; Stratford & Adams, 1977) and in vivo (Brown, 1975), little information is so far available on explicit cell-cycle-inhibitory effects. It has been shown (Stratford & Adams, 1977; Miller & Hall, 1978) that cell growth, scored as increase in cell number with time, was almost zero in populations exposed to 5 mm MIS under aerobic conditions. The present investigation shows that exposure to MIS under aerobic conditions has cell-cycle-inhibitory effects in human NHIK 3025 cells cultivated in vitro
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