Kawata, T., Ito, H., Saito, M., Uno, T., Okayasu, R., Liu, C., Kan'o, M., George, K. and Cucinotta, F. A. Caffeine Sensitizes Nondividing Human Fibroblasts to X Rays by Inducing a High Frequency of Misrepair. Radiat. Res. 164, 509–513 (2005).

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 normal human fibroblast 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 24 h treatment with caffeine. Analysis of chromosome aberrations using FISH (fluorescence in situ hybridization) 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.