Enhancement of radiation response on human carcinoma cells in culture by pentoxifylline

Purpose: Pentoxifylline, a methylxanthine, has been shown to improve tumor tissue oxygenation in hypoxic murine tumors and prevent the late radiation injury of normal tissues in mice. The present cell culture studies were carried out to determine whether pentoxifylline would enhance the cellular radiation response of several human carcinoma cells in culture under various culture conditions. Methods and Materials: Experiments were carried out with three human carcinoma cells grown in Eagle's MEM supplemented with 10% FCS. Cell survival was assayed by the colony forming ability of single plated cells to obtain dose-survival curves. Results: Cells irradiated and exposed to pentoxifylline for 24 hr showed a significant enhancement of radiationinduced cytotoxicity. Pre-irradiation treatment with the drug did not change cellular response to radiation. The magnitude of radiation enhancement was dependent on the concentration of drug and exposure time up to the time corresponding to one cell cycle time. Among the three human carcinoma cells used (HeLa S-3 cervix carcinoma, MCF-7 breast carcinoma, and HT-29 colon carcinoma), HeLa S-3 cells were most susceptible to the combined treatment with the enhancement ratio of 1.4 at 1 mM. Among the derivatives of methylxanthines, caffeine and pentoxifylline were equally effective on a molar basis. The combined effect of pentoxifylline and purine nucleosides, including guanosine and deoxguanosine, further enhanced the sensitizing effect of pentoxifylline. Conclusion: The present data along with other radiobiological effects of the drug suggest that pentoxifylline should be considered as a radiation enhancer for clinical radiotherapy.