title: The modification of hemoglobin affinity for oxygen and tumor radiosensitivity by antilipidemic drugs.
abstract: It has been recognized for some time that alterations in the affinity of Hb for oxygen could offer a means of improving oxygen delivery to tumors and achieving radiosensitization. Three antilipidemic drugs, clofibrate, bezafibrate, and gemfibrozil, two of which had previously been shown to reduce Hb/O2 affinity in vitro, were tested in mice for their ability to affect Hb/O2 affinity and to alter the radiosensitivity of the RIF-1 sarcoma. Each of the drugs produced a significant increase in the P50 of the blood, from a mean control value of 45 mm Hg to 55, 74, and 51 mm Hg after a dose of 1 g/kg of clofibrate, bezafibrate, and gemfibrozil, respectively. However, they had very different effects on the radiosensitivity of the RIF-1 tumor. When the mice breathed air at the time of irradiation, clofibrate produced a marked sensitization equivalent at the optimum time to a 20-fold reduction in hypoxic fraction; bezafibrate gave a lower sensitization equivalent to a 4-fold reduction, while gemfibrozil caused dramatic radioresistance equivalent to a 10-fold increase in hypoxic fraction. When the mice were given 95% O2/5% CO2 to breathe at the time of irradiation to ensure complete Hb saturation in the lungs, a large increase in the sensitization by bezafibrate was seen, but there was only a small change with clofibrate. We conclude that drugs which reduce Hb/O2 affinity could have a role in sensitizing tumors to radiation.
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000627:therapeutic use; D002994:Clofibrate / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015248:Gemfibrozil; D006454:Hemoglobins / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000378:metabolism*; D010421:Pentanoic Acids / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy*
chemical_list: D006454:Hemoglobins; D000960:Hypolipidemic Agents; D010421:Pentanoic Acids; D011838:Radiation-Sensitizing Agents; D002994:Clofibrate; D015248:Gemfibrozil; D010100:Oxygen; D001629:Bezafibrate