SYNERGISTIC INTERACTION OF PHOTODYNAMIC TREATMENT WITH THE SENSITIZERALUMINUM PHTHALOCYANINE AND HYPERTHERMIA ON LOSS OF CLONOGENICITY OF CHO CELLS

When CHO cells were exposed to hyperthermia and subsequently to photod ynamic treatment, the combined effects were additive but in the revers e sequence the interaction was synergistic. The synergistic interactio n comprised two quite different components: (1) photodynamically induc ed sensitization of cellular proteins and/or supramolecular structures for thermal inactivation and (2) a photodynamically induced inhibitio n of the cellular repair system for sublethal thermal damage, The firs t component of the synergistic interaction was reflected by a change o f the Arrhenius parameters of thermal cell killing, A lowering of the activation energy of this process was responsible for the synergistic interactions, whereas a concomitant decrease of the frequency factor, opposing this effect, actually caused a much lower degree of synergism at higher temperatures, This component of the synergistic interaction did not respond to the insertion of an intermediate incubation period between the two treatments, The second component of the synergistic i nteraction, viz the interference with the ability of cells to survive sublethal thermal damage, was reversible, as an intermediate incubatio n between photodynamic treatment and hyperthermia resulted in its repa ir, The photodynamically induced inhibition of the ability of cells to survive sublethal thermal damage was not related to ATP or glutathion e depiction, inhibition of dp novo protein synthesis or impairment of degradation of damaged protein molecules, Restoration of the repair sy stem for sublethal damage depended on a metabolic process and required free intracellular Ca2+, suggesting that a cell signaling pathway may be involved, Thus, in a practical sense the magnitude of the synergis tic interaction between photodynamic treatment and hyperthermia depend s on the length of the interval between the two treatments and on the temperature and duration of the subsequent thermal treatment, This may have significant consequences for the development of clinical protoco ls for the combined application of photodynamic therapy and hypertherm ia in the treatment of tumors.