Modulation of X ray DNA damage by SR-2508 +/- buthionine sulfoximine
It has been demonstrated that glutathione (GSH) depletion with buthionine sulfoximine (BSO) potentiates SR-2508 radiosensitization in hypoxic cells. We have measured the effect of SR-2508 alone, BSO alone, and combined treatment on radiation-induced DNA strand breaks in hypoxic V79 cells using alkaline and neutral elution. DNA base damage recognized by a damage specific endonuclease from M. luteus was also studied. Hypoxic irradiation markedly reduces the efficiency of single-strand (SSB) and double-strand breaks (DSB) to 10-20% compared to oxic irradiation. Hypoxia had less effect on the efficiency of base damage (ESS). BSO treatment alone, resulting in GSH depletion to less than 5% of controls, had little effect of hypoxic-SSB, DSB, and ESS. SR-2508 (5 mM) treatment alone in hypoxic cells increased the number of SSB, DSB and ESS to approximately half of that resulting from oxic irradiation. However, the combination of BSO and SR-2508 in hypoxic cells resulted in SSB and DSB comparable to oxic irradiation. This combined treatment resulted in less effect on ESS. We conclude that the observed hypoxic radiosensitization, using clonogenic survival assays with combined BSO-SR-2508, correlates with our results assessing DNA strand breaks and base damage.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 5005960
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 7
- Country of Publication:
- United States
- Language:
- English
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DNA
STRAND BREAKS
RADIOSENSITIZERS
RADIOSENSITIVITY EFFECTS
ANOXIA
FIBROBLASTS
GLUTATHIONE
HAMSTERS
IN VITRO
X RADIATION
ANIMAL CELLS
ANIMALS
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RODENTS
SOMATIC CELLS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)