ABSTRACT
A new class of substances exhibiting radioprotective and radiosensitizing effects depending on the concentration of the substance has been found. The radioprotective effect is probably due to the resonant absorption of radiation energy and its transformation into low-energy forms, as well as reactions with water radiolysis products. We studied the effects of 2,5-difeniloxazole and di[2-(5-feniloxazolil)]benzene in various concentrations in conjunction with irradiation on the growth of melanoma B-16 in mice and the average time of their lives. When using individual doses of irradiation and doses of preparations, we observed an increase in the average lifetime of mice and a reduced tumor size. These data allow us to conclude about the possibility of using these substances in the radiotherapy of tumors.
Subject(s)
Benzene Derivatives/pharmacology , DNA/drug effects , Oxazoles/pharmacology , Radiation-Protective Agents/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Benzene Derivatives/chemistry , Cell Membrane/drug effects , Cell Membrane/radiation effects , DNA/radiation effects , DNA Breaks, Double-Stranded/drug effects , Dose-Response Relationship, Radiation , Melanoma, Experimental , Mice , Mice, Inbred BALB C , Oxazoles/chemistry , Radiation-Protective Agents/chemistry , Radiation-Sensitizing Agents/chemistry , Spleen/cytology , Spleen/drug effects , Spleen/radiation effects , Water/chemistry , Whole-Body IrradiationABSTRACT
The ability of 2,5-diphenyloxazole (DPO) to modify biological consequences of the X-rays irradiation of mice was studied with a dose of 16 cGy at the administration of the agent in a wide range of concentrations before or after irradiation was studied. It was shown that the administration of the agent in doses 9.9 x 10(-3)-9.8 mg/kg 35-60 min before irradiation causes a reliable decrease in the spleen mass within 1 month after the action; for the dose 1 mg/kg, it causes the tendency to decrease of the content of lipid peroxidation (LPO) products; the dose 9.8 mg/kg causes a decrease in the cell-free DNA amount in blood plasma of mice. The administration of DPO before irradiation causes changes in the scale and direction of the correlation between the DNA and LPO products contents in blood plasma of irradiated mice compared with the control. The administration of DPO 15-60 min after irradiation do not cause any reliable changes in the investigated parameters. The aviability of the study of the radioprotective properties of the DPO derivatives as agents with a nontraditional character of action is supposed.
Subject(s)
Oxazoles/pharmacology , X-Rays , Animals , DNA/blood , Dose-Response Relationship, Radiation , Female , Lipid Peroxidation , Mice , Spleen/drug effects , Spleen/radiation effectsABSTRACT
The effects of 2,5-diphenyloxazole ad its derivatives suggested as nontraditional radioprotectors on mice spleen DNA structure were studied. The effects of these compounds were studied on intraperitoneal injection with and without subsequent X-ray exposure of mice to a dose of 12 cGy. The formation of double-strand breaks and DNA conformation change (by adsorption on NC filters) were recorded. A genotoxic effect of 2,5-diphenyloxazole and its derivatives, a nonlinearity of their dose-response relationships and different effects depending on the substance concentration were found. Some of the compounds exhibited radioprotective properties in certain concentration.
Subject(s)
DNA/radiation effects , Mutagens/toxicity , Oxazoles/pharmacology , Radiation-Protective Agents/pharmacology , Animals , DNA/analysis , DNA/drug effects , DNA Damage , Female , Mice , Mice, Inbred BALB C , Mutagens/chemistry , Mutagens/pharmacology , Nucleic Acid Conformation/drug effects , Nucleic Acid Conformation/radiation effects , Oxazoles/chemistry , Oxazoles/toxicity , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/toxicity , Spleen/chemistry , Spleen/radiation effectsABSTRACT
Pentifin and dopamine D1 receptor antagonist SCH-23390 possess similar pharmacological properties. In the present work we studied in vitro effects of Pentifin on dopamine receptors. Experiments on rat ductus deferents showed that Pentifin acts as a weak ligand of dopamine receptors. Our results indicate that the antihaloperidol effect of Pentifin is not related to the blockade of dopamine receptors.
