The Action of Caffeine on X-Irradiated HeLa Cells. IV. Progression Delays and Enhanced Cell Killing at High Caffeine Concentrations

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Abstract
The response of X-irradiated and unirradiated HeLa S3 [human cervical cancer] cells to treatment with caffeine at concentrations between 1-10 mM was examined with respect to delay in progression through the cell generation cycle and enhancement of the expression of potentially lethal X-ray damage. Progression is delayed in a concentration-dependent fashion; the generation time is doubled at about 4 mM. The duration of G1 is lengthened and the rate of DNA synthesis is reduced, although the kinetics are different in the 2 phases: the rate of DNA synthesis is usually unaffected at 1 or 2 mM and no concentration threshold exists for the slowing of progression through G1. Progression through G2 is apparently unaffected by concentrations up to at least 10 mM. Killing of irradiated cells in G2 is somewhat greater after treatment with the higher caffeine concentrations than reported previously for 1 mM. An additional mode of killing is observed in irradiated G1 cells which previously were only slightly affected by 1 mM caffeine; they suffer extensive killing at concentrations above 5 mM. The time-survival curves for irradiated, caffeine-treated G1 and G2 cells have characteristically different shapes. The dose-survival curves for cells treated with the higher caffeine concentration display steeper terminal slopes and narrower shoulders.