The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice.

An experiment was performed to test the effectiveness of pentoxifylline in reducing late radiation injury. One hundred and four C3H mice were randomized into eight groups of 13 mice each, and the right hind limbs were irradiated with 4000, 5000, 6000, or 7000 cGy in ten fractions. Each group was treated with once daily injections of either pentoxifylline or saline for 30+ weeks. An additional ten mice received daily injections of pentoxifylline or saline, but no irradiation. The pentoxifylline animals demonstrated significantly less late injury than the saline treated animals. The most obvious differences were observed in the 5000 and 6000 cGy groups. There were seven radiation related deaths in the saline treated control groups, but only one radiation related death in the pentoxifylline treated groups. Whereas 42% (20/48) of the saline treated animals had a late injury score of 3.0 or greater, only 8% (4/51) of the pentoxifylline treated animals had a late skin score as high as 3.0. Pentoxifylline had no effect on the acute radiation injury scores. The drug was well tolerated with no toxic effects noted. Pentoxifylline is a methyl xanthine derivative that is used to treat vascular occlusive disease in humans. It improves perfusion through small capillaries by improving the deformability of red blood cells, inhibiting platelet aggregation, and stimulating the release of prostacyclin. This study shows that the prophylactic administration of pentoxifylline can modify late radiation induced injury in the mouse extremity. It may have value in the prevention or treatment of late radiation induced injury in humans, and it could be a useful tool to help define the mechanisms of late radiation injury in specific organs.