Enhancement of misonidazole radiosensitization by buthionine sulphoximine.
The influence of glutathione (GSH) depletion on the radiation response and on the radiosensitizing efficiency of misonidazole (miso) has been studied in two types of mouse tumour and in mouse skin. Buthionine sulphoximine (BSO) has been administered in a variety of regimes, leading to a maximal depletion of GSH to 37% of control values in one tumour (CA MT) and 61% in the other (SA FA). Pretreatment with BSO did not alter the radiosensitivity of either tumour when treated with X-rays. It had a slight effect on the sensitizing efficiency of miso, corresponding to a factor less than three, which was detectable only at the highest X-ray doses used. No enhancement of miso efficiency was seen with 5 daily fractions. Prolonged administration of BSO resulted in a slight radiosensitization of mouse skin. When combined with miso the effect was very small and was only detectable at high X-ray doses. BSO however produced a marked enhancement of the acute toxicity of miso, as judged by lethality after large single doses.
D000818:Animals; D019328:Buthionine Sulfoximine; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D005978:Glutathione / Q000502:physiology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008920:Misonidazole / Q000494:pharmacology* / Q000633:toxicity; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000528:radiation effects
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; D005978:Glutathione