Evaluation of nitroimidazole hypoxic cell radiosensitizers in a human tumor cell line high in intracellular glutathione
Five nitroimidazole hypoxic cell radiosensitizers were evaluated in a human lung adenocarcinoma cell line (A549) whose GSH level was 8-fold higher than Chinese hamster V79 cells. One millimolar concentrations of Misonidazole (MISO), SR-2508, RSU-1164, RSU-1172, and Ro-03-8799 sensitized hypoxic A549 cells to radiation, with Ro-03-8799 giving the highest sensitizer enhancement ration (SER) (2.3). However, MISO, SR-2508 and Ro-03-8799 were less effective in this cell line than in V79 cells, presumably due to higher GSH content of the A549 cells. Increased hypoxic radiosensitization was seen with 0.1 mM Ro-03-8799 after GSH depletion by BSO as compared to 0.1 mM Ro-03-8799 alone (SER-1.8 vs 1.3). The combination of GSH depletion and 0.1 mM Ro-03-8799 was considerably more toxic than 0.1 mM or 1.0 mM Ro-03-8799 alone. This sensitivity was much greater than has been observed for SR-2508. These data show that Ro-03-8799 was the most efficient hypoxic cell radiosensitizer in a human tumor cell line considerably higher in GSH than the rodent cell lines often used in hypoxic radiosensitization studies. Thus, Ro-03-8799 may be a more effective hypoxic cell sensitizer in human tumors that are high in GSH.
- Research Organization:
- National Cancer Institute, Bethesda, MD (USA)
- OSTI ID:
- 6253742
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 16:4
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mechanisms of hypoxic cell radiosensitization and the development of new sensitizers
Variation in sensitizing efficiency for SR 2508 in human cells dependent on glutathione content
Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
RADIOSENSITIZERS
EVALUATION
ANOXIA
CARCINOMAS
GLUTATHIONE
MAN
MISONIDAZOLE
OXYGEN
TUMOR CELLS
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
DISEASES
DRUGS
ELEMENTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
NEOPLASMS
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
550603 - Medicine- External Radiation in Therapy- (1980-)