ABSTRACT
A high efficacy of the combined use of nontoxic doses of two pharmaceuticals: cystamine (50 mg/kg) and mexamine (25 mg/kg) under the conditions of short-term exogenous hypoxia (7.5% O2) was found in (CBA X C57Bl)F1 mice. The dose modification factor using the survival rates was 2.56.
Subject(s)
Oxygen , Radiation Protection , Whole-Body Irradiation , 5-Methoxytryptamine/administration & dosage , Animals , Cystamine/administration & dosage , Male , Mice , Radiation DosageABSTRACT
The authors have shown that a more pronounced antitumor effect of radiation in the combined use of metronidazole and induced short-term hyperglycemia (STH) may result not only from the summation of the two effects: the sensitizing effect of metronidazole and decreased viability of irradiated cells caused by STH but also from the intensified cytotoxic effect of metronidazole on hypoxic tumor cells. It was also noted that when hypoxic cells subjected to the sensitizing effect of electron acceptor sensitizers are found in the normal and tumorous tissues (skin), STH use following irradiation in the presence of metronidazole enhances selectively the tumor radiation effect.
Subject(s)
Carcinoma, Ehrlich Tumor/radiotherapy , Glucose/administration & dosage , Metronidazole/administration & dosage , Radiation Tolerance , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/metabolism , Combined Modality Therapy , Mice , Oxygen Consumption/drug effects , Oxygen Consumption/radiation effects , Radiation Injuries, Experimental , Radiotherapy Dosage , Skin/radiation effectsABSTRACT
The appropriateness of the combined use of electron acceptor radiosensitizers: 4-nitroimidazole and metronidazole, and sulfhydryl protectors WR-2721 (gammaphos) and cysteamine was shown on the Chinese hamster cells V-79 and transplantable mouse tumors. The administration of the sensitizer 30-60 min and the protector 15-20 min before the irradiation of solid tumors weakens radiation reactions of the skin (metronidazole plus gammaphos) without weakening the effect of radiosensitization on transplantable animal tumors (metronidazole plus gammaphos or 4-nitroimidazole plus WR-2721).
Subject(s)
Neoplasms, Experimental/radiotherapy , Radiation-Protective Agents/administration & dosage , Radiation-Sensitizing Agents/administration & dosage , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/radiotherapy , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/mortality , Carcinoma, Ehrlich Tumor/radiotherapy , Cell Line , Cell Survival/drug effects , Cell Survival/radiation effects , Cricetinae , Cricetulus , Drug Therapy, Combination , Female , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/mortality , Mammary Neoplasms, Experimental/radiotherapy , Mice , Mice, Inbred C3H , Neoplasm Transplantation , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/mortality , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/prevention & control , Radiotherapy DosageABSTRACT
The authors showed the absence of differences in the value of a protective effect of gammaphos at doses of 0.25 and 0.5 mM/kg (67 and 134 mg/kg) evaluated by the survival of mice irradiated in the air and while breathing a gaseous mixture containing 10% O2; the dose modifying factor (DMF) was 1.15 and approximately equal to 1.3, respectively. During irradiation of mice under conditions of normal oxygenation and while breathing hypoxic gaseous mixtures containing 10 and 8% O2 no differences were found in the level of an antiradiation effect of gammaphos at a dose of 1mM/kg (268 mg/kg); the DMF of gammaphos in all the cases was 1.6. During a short-term hard hypoxia (6.5% O2, DMF = 2.01), the protective effect of gammaphos is somewhat lower (DMF = 1.41) perhaps as a result of the modification limits in radiosensitivity because the DMF in the combination of both factors (gammaphos + 1 min. of 6.5% O2) equals 2.84. The DMF of gammaphos under the conditions of 20 min hypoxia (6.5% O2) producing a lesser radioprotective effect (DMF-1.48) equals 1.6, i. e. the value of the gammaphos protective effect in this case does not differ from that during irradiation of mice in the air. The data obtained lead to a conclusion of the independence of the value of the gammaphos protective effect on the level of the oxygenation of cells and tissues of irradiated objects.
Subject(s)
Amifostine/therapeutic use , Organothiophosphorus Compounds/therapeutic use , Oxygen/pharmacology , Radiation Injuries, Experimental/prevention & control , Whole-Body Irradiation , Animals , Male , Mice , Radiation Dosage , Time FactorsABSTRACT
The radiosensitizing effect of metronidazole is most pronounced in conditions of acute hypoxia (mature mice, 5% O2) or anoxia (neonatels, 100% N2) and decreases with increasing O2 content in a gas mixture. The preparation is less effective in neonatal mice, adapted to oxygen deficiency, than in mature animals. The data obtained are discussed with respect to the problem of overcoming the radioresistance of tumours that is conditioned by hypoxic cells.
Subject(s)
Aging/radiation effects , Metronidazole/pharmacology , Radiation-Sensitizing Agents/pharmacology , Adaptation, Physiological/drug effects , Adaptation, Physiological/radiation effects , Aging/drug effects , Animals , Animals, Newborn , Female , Gamma Rays , Hypoxia/physiopathology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Time FactorsSubject(s)
Metronidazole/pharmacology , Oxygen , Radiation-Sensitizing Agents/pharmacology , Animals , Mice , Time FactorsABSTRACT
Studies of 5-day mice F1 (CBA X C57Bl) demonstrated that an exposure of animals to acute hypoxia (5% O2--95% N2) during their irradiation produced a different effect on the spleen and the growing cerebellar cortex. In these circumstances lesions of well oxygenated spleen tissues were noticeably reduced, whereas cerebellar cortex cells characterized by a low oxygen tension and a high tolerance to anoxia remained essentially unprotected. The findings are discussed in the light of adaptation concepts postulating that oxygen tension in cells is regulated, depending on the level of its uptake which in turn is determined by the relative oxygen content in the surrounding medium.