Modification of SR 2508 sensitization in hypoxic V79 cells by manipulation of glutathione levels.
This series of experiments employed the hypoxic cell sensitizer SR 2508 in concentrations ranging from 0.1 to 10 mM and V-79 cells irradiated in air or made hypoxic in glass syringes, then irradiated with 15 MV X rays. Using a series of survival curves measured at the various concentrations, K curves relating sensitizer enhancement ratio (SER) to SR 2508 concentration were calculated with normal GSH levels or with depletion of GSH to 0% using 1 mM buthionine sulfoximine (BSO) or elevation to 200% of normal using 1 mM oxothiazolidine carboxylate (OTZ). Survival curves were fitted by computer, allowing calculation of standard errors for the SER values. The depletion of GSH by BSO sensitized hypoxic and aerated cells significantly and caused more than additive enhancement of SR 2508 sensitization in hypoxic cells. Elevation of GSH with OTZ protects cells irradiated in air or hypoxia and reduces the SER obtained with SR 2508. The results further support the importance of GSH levels in influencing sensitization by nitroimidazoles.
Phillips
T L
TL
Radiation Oncology Branch, National Cancer Institute.
Mitchell
J B
JB
DeGraff
W G
WG
Russo
A
A
Albright
N
N
Rajpal
R
R
D000818:Animals; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D017341:Etanidazole; D005978:Glutathione / Q000502:physiology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D013844:Thiazoles; D053778:Thiazolidines; D008717:Methionine Sulfoximine; D017341:Etanidazole; D019328:Buthionine Sulfoximine; D005978:Glutathione; D010100:Oxygen; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid