Enhancement of SR 2508 (etanidazole) radiosensitization by buthionine sulphoximine at low-dose-rate irradiation.
SR 2508 (etanidazole) (1 mM) or buthionine sulphoximine (BSO, 50 microM) or both drugs together did not radiosensitize oxic V79 Chinese hamster cells irradiated at either an acute dose rate (2.35 Gy/min) or at a low dose rate (0.117 Gy/min). BSO pretreatment (15 h at 37 degrees C) depleted cellular glutathione (GSH) to less than or equal to 1% of control level and radiosensitized hypoxic cells at both dose rates with an enhancement ratio (ER) of 1.2. SR 2508 alone radiosensitized hypoxic cells equally at both dose rates with an ER of 1.5. However, ER values of 2.2 and 2.5 were obtained with 1 mM SR 2508 in GSH-depleted cells at acute and low dose rate, respectively, with no significant difference between the two, i.e. there is no dose rate dependence for this potentiation. Since BSO increases SR 2508 radiosensitization and the combined BSO + SR 2508 treatment is extremely cytotoxic to hypoxic cells, our results suggest that combining BSO with SR 2508 will be useful in brachytherapy as well as external-beam therapy if the toxicity from both drugs in vivo is less than the gain in radiosensitization achieved.
Wong
R S
RS
Department of Radiation Oncology, University of California, San Francisco 94143.
Basas
R A
RA
Ling
C C
CC
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage*; D019328:Buthionine Sulfoximine; D015687:Cell Hypoxia / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004357:Drug Synergism; D017341:Etanidazole; D066298:In Vitro Techniques; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009593:Nitroimidazoles / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*
D000963:Antimetabolites; D004338:Drug Combinations; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D017341:Etanidazole; D019328:Buthionine Sulfoximine