The effect of hyperthermia on murine leukaemia cells in combination with photodynamic therapy

Mouse leukaemia L1210 cells were subjected to hyperthermia (43.0 +/- 0.05 degrees C, water bath) and photodynamic therapy (50 micrograms/ml haematoporphyrin derivative (HpD), 630 +/- 5 nm at 0.1 mW/cm2) for varying lengths of treatment time in different sequences. Dose-response curves showed that the two modalities interact to make the combination more cytotoxic than the sum of the separate individual treatments, and that a determining factor is the intracellular concentration of HpD of tumour cells during hyperthermia. High cytotoxic (synergistic) effects of photodynamic therapy (PDT) were obtained when PDT was performed after hyperthermia following HpD administration. However, only additive cytotoxic effects were found, when hyperthermia was performed after HpD administration and PDT. These cytotoxic data were supported by DNA damage (the increase in single-stranded DNA) as revealed by flow cytometry in cells stained with acridine orange (AO). These in vitro experiments suggest that clinical applications of PDT after hyperthermia with HpD injection might be useful.