Radioprotective action of WR-1065 on radiation-induced DNA strand breaks in cultured Chinese hamster ovary cells
We have examined the radioprotective effect of WR-1065 on cultured Chinese hamster ovary cells. The effects of the drug on the induction and rejoining of gamma-ray-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) were measured using alkaline (pH 12.1) and neutral (pH 7.0) elution, respectively. Molecular protection factors (PFs) calculated from these data allowed us to determine whether the degree of modification of strand breakage accurately predicted the PFs measured using the biological end point of cell survival. The drug did protect against the induction of both SSBs and DSBs, although to an extent that did not appear to fully account for the degree of radioprotection in terms of cell killing measured under identical conditions. It is therefore unlikely that radioprotection by WR-1065 occurs simply as a consequence of a general lowering of all types of gamma-ray-induced DNA lesions, and it is possible that the drug could differentially protect against the induction of subsets of these DNA lesions. The rate of SSB rejoining was retarded following preirradiation treatment of cells with WR-1065, but there was no effect on DSB rejoining. Postirradiation treatment with WR-1065 also appeared to retard SSB rejoining but without an accompanying effect on either DSB rejoining or cell survival; however, this effect was largely reversed by the addition of catalase and was, therefore, probably a result of H/sub 2/O/sub 2/ generated by autoxidation of the drug. Based on these observations, it would appear that the molecular actions of aminothiol radioprotective compounds that lead to reduced cell killing are much more complex than previously thought.
- Research Organization:
- Univ. of Texas System Cancer Center, Houston (USA)
- OSTI ID:
- 5380099
- Journal Information:
- Radiat. Res.; (United States), Vol. 113:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHO CELLS
GENETIC RADIATION EFFECTS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
STRAND BREAKS
RADIOINDUCTION
CELL KILLING
DNA
DNA REPAIR
GAMMA RADIATION
HAMSTERS
HYDROGEN PEROXIDE
SURVIVAL CURVES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DRUGS
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
HYDROGEN COMPOUNDS
IONIZING RADIATIONS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEROXIDES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
RODENTS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture