Both hyperthermia and photodynamic therapy of cancer are frequently used in combination with other treatment modalities in order to improve tumor control with minimal damage to normal tissues. The present results indicate that the most effective combination of treatment modalities is different in different cell types. For instance, ionizing irradiation and hyperthermia exhibited additivity when applied to L929 fibroblasts, in contrast to the synergistic interaction described before in many other cell lines. This aberrant behavior of L929 cells could be explained by the relative insensitivity of DNA repair in these cells to hyperthermia. Conversely, a synergistic interaction between photodynamic treatment and ionizing irradiation was observed with L929 fibroblasts, whereas these treatments were additive with Chinese hamster ovary and T24 cells. The synergistic interaction with L929 cells could be explained by the high sensitivity of DNA repair in these cells to photodynamic treatment. Photodynamic treatment and hyperthermia exhibited a synergistic interaction in L929, Chinese hamster ovary, and T24 cells. The critical target for cell killing by the combined treatment protocol in these cell lines has not yet been elucidated. In all three cell lines, however, analysis of the results according to the Arrhenius equation revealed a photodynamically induced change of both the frequency factor and the activation energy of subsequent thermal cell killing. It is considered that this may indicate a basic mechanism, in which a particular protein is a common, critical target of the two modalities of treatment.

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This work was supported by the Netherlands Cancer Foundation (Grant IKW 89-01).

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