Strand break repair, DNA polymerase activity and heat radiosensitization in thermotolerant cells

Abstract

HeLa S₃ cells were made thermotolerant by ‘chronic’ (5 h at 42°C) or ‘acute’ (15 min at 44°C followed by 5 h at 37°C) heat treatments. Cell survival, repair of radiation-induced DNA strand breaks, α and β DNA polymerase activity and radiation sensitivity following hyperthermia were all measured in both control and thermotolerant cells.

The ability to repair DNA strand breaks correlated well with cell survival following hyperthermia. Hyperthermic inhibition of strand break repair was reduced in thermotolerant relative to control cells, although the thermal tolerance ratios for repair were less than for hyperthermic cell killing.

Both radiosensitization and DNA polymerase inactivation by hyperthermia were only slightly reduced in thermotolerant relative to control cells. Hence a poor correlation was found between these two parameters and hyperthermic cell survival. For all heat treatments applied, α and β DNA polymerase activity correlated well with the extent of hyperthermic radiosensitization.

Key Words:

• hyperthermia
• thermotolerance
• radiosensitization
• DNA polymerase
• DNA strand breaks
• DNA repair
• (HeLa cells)