The effect of hyperthermia on DNA repair.

In the past there were many individual observations on the value of hyperthermia in the treatment of human neoplasia but most of the information about the value of hyperthermia as a single agent or in the combined modality approach has come from laboratory investigations. Dose response curves for cell survival after exposure to heat are similar in shape to cell survival curves obtained after irradiation or treatment with some cytostatic agents. The shoulder in such curves suggests that repair of sublethal or potentially lethal damage takes place after hyperthermic treatment. On the level of molecular biology the process of cellular repair should correspond to repair of damage inflicted on deoxyribonucleic acid (DNA). We have shown by means of the BUdR assay that such DNA-repair synthesis does take place upon exposure to heat. Many investigations have provided evidence of a synergism between hyperthermia and ionizing irradiation or some cytostatic agents. It was suggested that such synergism might be caused by the inhibition of repair of sublethal damage by heat. After inflicting DNA damage by a strong alkylating agent (NA-AAF) we could demonstrate DNA-repair synthesis by means of the BUdR-assay during exposure to heat. At the present time results obtained by assaying DNA repair on the basis of cell survival and by means of the BUdR-assay are difficult to reconcile.