Caffeine sensitizes nondividing human fibroblasts to X rays by inducing a high frequency of misrejoining

Abstract

Caffeine sensitizes cells to ionizing radiation, and this effect is believed to be associated with the disruption of DNA damage-responsive cell cycle checkpoints, which is controlled by ATM. Recent studies suggest that misrejoining of DSBs is one of the underlying mechanisms of AT cell hyper-radiosensitivity. In this study, we investigated the effects of caffeine and radiation on nongrowing G0 AT hetero cells by determining cell survival and scoring aberrations in calyculin A-induced G2 chromosomes. Results from the cell survival study indicate that after X-ray exposure G0 cells were sensitized by 24h treatment with caffeine. Analysis of chromosome aberrations using FISH revealed a high frequency of aberrant cells and color junctions in the caffeine-treated cells. Since most DNA repair in nongrowing G0 cells is believed to result from nonhomologous end joining(NHEJ), caffeine may influence the fidelity of the NHEJ pathway in irradiated G0 cells.