RESUMO
Radiation-chemical reductions have been carried out with several nitroimidazoles. Reduction of these drugs in the presence of single-stranded phi chi 174 DNA causes extensive lethal damage. However, relatively stable (end) products, do not contribute to the damage, although glyoxal is potentially toxic. This demonstrates that a short-lived intermediate in the reduction process is responsible. Further, the quantity of damage in the DNA depends on both dose (reduction)-rate and also the nature of the drug.
Assuntos
Colífagos , DNA Viral , Nitroimidazóis/farmacologia , DNA de Cadeia Simples , Metronidazol/farmacologia , Metronidazol/efeitos da radiação , Misonidazol/farmacologia , Misonidazol/efeitos da radiação , Nitroimidazóis/efeitos da radiação , Ornidazol/farmacologia , Ornidazol/efeitos da radiação , Oxirredução , RadioquímicaRESUMO
The effect of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single-stranded phi X174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA.
Assuntos
DNA , Nitroimidazóis , Radiossensibilizantes , Bacteriófago phi X 174 , DNA de Cadeia Simples , DNA Viral , Eletrólise , OxirreduçãoRESUMO
The effect of misonidazole and cytochrome c on biologically active DNA was studied. In a solution of single-stranded phi X174 DNA the presence of both sensitizer and cytochrome c is needed to evoke radiosensitization. However, sensitizer or cytochrome c alone protects the DNA. Cytochrome c offers even an extra protection. The sensitization is dependent on the concentration of misonidazole. This finding opens up the possibility of studying sensitizers in a relatively simple system.
Assuntos
Bacteriófago phi X 174 , Grupo dos Citocromos c/farmacologia , DNA de Cadeia Simples/efeitos da radiação , DNA Viral/efeitos da radiação , Misonidazol/farmacologia , Nitroimidazóis/farmacologia , Oxigênio/fisiologia , Radiossensibilizantes/farmacologia , Radioisótopos de Cobalto , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Raios gama , Fenol , Fenóis/farmacologia , Protetores contra Radiação/farmacologiaRESUMO
The effect of heat treatment (45 degrees C) on gamma-irradiated biologically active single-stranded phi X174 DNA, dissolved in a bacterial extract, was studied. The results show that under these circumstances heat-sensitive damage is found, which is absent after irradiation in pure buffer. The damage is non-lethal and probably becomes an apurinic/apyrimidinic site, which is lethal, upon the post-irradiation heat treatment. Prolonged heating converts it into a break. The amount of the initial damage depends on the conditions of irradiation.
