Effects of Caffeine on X-irradiated Synchronous, Asynchronous and Plateau Phase Mouse Ascites Cells: The Importance of Progression Through the Cell Cycle for Caffeine Enhancement of Killing

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Abstract
Summary The effects of caffeine on X-irradiated synchronous, exponential and plateau phase cell populations was studied. Caffeine was found to potentiate the killing effect of X-rays on exponentially growing cells giving rise to exponential survival curves (D0 = (0·8 ± 0·05)Gy) at 4mM and 14 hours treatment, presumably by expressing X-ray induced potentially lethal damage (PLD). Irradiated plateau phase cells were found to be less sensitive to caffeine. Exponentially growing cells also became less sensitive to the effects of caffeine when they were incubated in the conditioned medium of plateau phase cells (C-medium) in which cell growth was considerably inhibited. Low caffeine concentrations (2 mM) also enhanced X-ray induced killing of cells irradiated in G1−, G1/S- or S-phase, but more effectively enhanced the killing of G2-phase cells. High caffeine concentrations (6 mM) enhanced killing of cells in all phases of the cell cycle. Incubation of synchronized populations in C-medium during treatment with caffeine (both 2 mM and 6 mM) resulted in less potentiation than in cells treated in fresh medium. The expression of X-ray induced PLD caused by 6 mM caffeine in cells irradiated in various phases of the cell cycle resulted in an exponential survival curve with a mean lethal dose D0 = (0·8 ± 0·05) Gy but the time of caffeine treatment necessary to reach this curve was different for cells irradiated in different phases of the cell cycle. The repair of PLD, measured as loss of sensitivity to 6 mM caffeine (4 hours treatment) was of 1–2 hours duration.