The Action of Caffeine on X-Irradiated HeLa Cells. II. Synergistic Lethality

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Abstract
Postirradiation treatment of HeLa S3 [human cervical cancer] cells with 1 mM caffeine results in a marked diminution of the surviving fraction as scored by colony formation. The decrease is dose dependent. The effect of a 24 h postirradiation treatment of a nonsynchronous population with caffeine is to change the terminal slope of the survival curve and its intercept. D0 is reduced from 130 to 60 rad; the extrapolation number is increased about 2-fold. The amount of postirradiation killing is maximal if cells are exposed to caffeine at a concentration of at least 1 mM for 8 h; < 10% of unirradiated cells are killed under these conditions. Dose-response curves were also obtained for synchronous cells at various phases of the cell cycle. Similar results were obtained at all cell ages, but the magnitude of the effect is age dependent. This age dependence was further explored in experiments in which mitotically collected cells were exposed to 300 or 500 rad doses at 2 h intervals throughout the cell cycle. Treatment with caffeine for 24 h after irradiation enhances the killing of cells late in the cycle more than cells in G1. The sensitivities of 2 other cell lines, CHO [Chinese hamster ovary] and EMT6 [rat mammary tumor] were also examined. Both are substantially less sensitive to caffine. The smaller cell cycle dependence of CHO cells is qualitatively the same as that of HeLa cells.