Inhibition of repair of X-ray-induced DNA damage by heat: the role of hyperthermic inhibition of DNA polymerase alpha activity
HeLa S3 cells growing in suspension have been used to investigate possible mechanisms underlying the inhibitory action of hyperthermia (44 degrees C) on the repair of DNA strand breaks as caused by a 6-Gy X-irradiation treatment. The role of hyperthermic inactivation of DNA polymerase alpha was investigated using the specific DNA polymerase alpha inhibitor, aphidicolin. It was found that both heat and aphidicolin (greater than or equal to 2 micrograms ml-1) could decrease DNA repair rates in a dose-dependent way. When the applications of heat and aphidicolin were combined, each at nonmaximal doses, no full additivity in effects was observed on DNA repair rates. When the heat and radiation treatment were separated in time by postheat incubation at 37/sup 0/C, restoration to normal repair kinetics was observed within 8 h after hyperthermia. When heat was combined with aphidicolin addition, restoration of the aphidicolin effect to control level was also observed about 8 h after hyperthermia. It is suggested that although DNA polymerase alpha seems to be involved in the repair of X-ray-induced DNA damage, and although this enzyme is partially inactivated by heat, other forms of heat damage have to be taken into account to explain the observed repair inhibition.
- Research Organization:
- State Univ. of Groningen, The Netherlands
- OSTI ID:
- 5840362
- Journal Information:
- Radiat. Res.; (United States), Vol. 112:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA POLYMERASES
ENZYME ACTIVITY
HELA CELLS
DNA REPAIR
GENETIC RADIATION EFFECTS
HYPERTHERMIA
RADIOSENSITIVITY EFFECTS
STRAND BREAKS
RADIOINDUCTION
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
HEAT
INHIBITION
X RADIATION
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY TEMPERATURE
ELECTROMAGNETIC RADIATION
ENERGY
ENZYMES
GENETIC EFFECTS
IONIZING RADIATIONS
NUCLEOTIDYLTRANSFERASES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
TRANSFERASES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture