The effect of in vivo GSH depletion on thermosensitivity, radiosensitivity and thermal radiosensitization.
The effect of glutathione (GSH) depletion on the interaction of hyperthermia (HT) and single-dose external-beam radiation delivered at conventional dose rates (RT) and low-dose-rate brachytherapy (BT) was examined in a murine mammary adenocarcinoma (MTG-B). Tumour volume growth delay from the day of treatment to double the treatment volume (GDDV) was used as the experimental end-point. The growth delay for radiation alone was greater when combined with GSH depletion, while this level of GSH depletion produced no effect on the BT alone or HT alone response. The synergism ratio (SR) was calculated for all HT and RT or HT and BT protocols at each dose. Although depletion did not increase the SR for external-beam treatments, the SR for HT and BT treatments was increased with GSH depletion.
Jones
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Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Douple
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D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D003131:Combined Modality Therapy; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006979:Hyperthermia, Induced; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D011836:Radiation Tolerance
D000963:Antimetabolites; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione