Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin.
The effectiveness of the radiosensitiser Ro-07-0582 has been tested in man by observing the skin reaction after irradiation using a radio-strontium source with and without administration of the drug. The skin reaction technique has been extended so that skin was irradiated when at low oxygen tension (hypoxic) as well as when fully oxygenated (oxic). Limbs have been made hypoxic by occlusion of the circulation using a sphygmomanometer cuff. To this has been added the prior use of an Esmarch's bandage to reduce the volume of blood in the skin and the enclosing of the limb in a bag of nitrogen. The Oxygen Enhancement Ratios obtained without the sensitiser in nine studies using this system ranged from 1-64 to 2-46. Using Ro-07-0582 skin reactions after oxic exposures were not enhanced but those after hypoxic exposures were markedly increased. The Relative Sensitising Efficiency expresses, as a percentage, the restoration of the sensitivity of cells protected by hypoxia. In six cases where Ro-07-0582 was given in doses ranging from 81 to 165 mg/kg, efficiencies ranged from 27 to 71%. These results can be compared with three studies using metronidazole where efficiencies ranged from 11 to 15%. Using comparable dosage Ro-07-0582 seems approximately three times more effective than metronidazole. In this first study in man, Ro-07-0582 appears to be a highly effective radiosensitiser of hypoxic cells.
D003250:Constriction; D004341:Drug Evaluation; D006801:Humans; D000860:Hypoxia / Q000209:etiology; D008795:Metronidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011829:Radiation Dosage; D011830:Radiation Effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012044:Regression Analysis; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D012880:Skin Pigmentation / Q000528:radiation effects; D013326:Strontium Radioisotopes
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D013326:Strontium Radioisotopes; D008795:Metronidazole; D010100:Oxygen