Hyperthermia can differentially modulate the repair of doxorubicin-damaged DNA in normal and cancer cells.

Abstract

Hyperthermia can modulate the action of many anticancer drugs, and DNA repair processes are temperature-dependent, but the character of this dependence in cancer and normal cells is largely unknown. This subject seems to be worth studying, because hyperthermia can assist cancer therapy. A 1-h incubation at 37 degrees C of normal human peripheral blood lymphocytes and human myelogenous leukemia cell line K562 with 0.5 microM doxorubicin gave significant level of DNA damage as assessed by the alkaline comet assay. The cells were then incubated in doxorubicin-free repair medium at 37 degrees C or 41 degrees C. The lymphocytes incubated at 37 degrees C needed about 60 min to remove completely the damage to their DNA, whereas at 41 degrees C the time required for complete repair was shortened to 30 min. There was also a difference between the repair kinetics at 37 degrees C and 41 degrees C in cancer cells. Moreover, the kinetics were different in doxorubicin-sensitive and resistant cells. Therefore, hyperthermia may significantly affect the kinetics of DNA repair in drug-treated cells, but the magnitude of the effect may be different in normal and cancer cells. These features may be exploited in cancer chemotherapy to increase the effectiveness of the treatment and reduce unwanted effects of anticancer drugs in normal cells and fight DNA repair-based drug resistance of cancer cells.