Lisofylline as a modifier of radiation therapy

Lisofylline is a new methylxanthine. The potential of lisofylline to enhance the response to ionizing radiation of the EMT-6 murine mammary carcinoma in vitro and in vivo was assessed and compared with pentoxifylline. Addition of lisofylline (100 microM) or pentoxifylline (100 microM) from the time of radiation exposure and throughout the time of colony formation did not alter the response of normally oxygenated EMT-6 cells to gamma-radiation delivered at 0.76 Gy/min or 12.3 Gy/min. The dose modifying factor for hypoxic EMT-6 cells by lisofylline or pentoxifylline and radiation delivered at 0.76 Gy/min was 2.3. Higher dose rate radiation (12.3 Gy/min) was more cytotoxic toward hypoxic EMT-6 cells than lower dose rate radiation. The dose modifying factor produced by lisofylline in the high dose rate radiation setting was 1.2. In vivo, using the tumor cell survival assay, lisofylline decreased the shoulder of the radiation survival curve (0.76 Gy/min) by a factor of 1.7 +/- 0.2 while pentoxifylline did not. In the tumor growth delay assay, administration of multiple doses of lisofylline or pentoxifylline along with single dose radiation (0.76 Gy/min) was 1.3, while the radiation dose modifying factor for lisofylline or pentoxifylline administered by continuous infusion was 1.5. Overall, lisofylline was a more effective modifier of gamma-radiation therapy than pentoxifylline, and further investigation of lisofylline in this setting is warranted.