TIME and SEQUENCE DEPENDENT INFLUENCE OF IN VITRO PHOTODYNAMIC THERAPY (PDT) SURVIVAL BY HYPERTHERMIA

Abstract— Experimental mouse mammary tumor cells (EMT-6) were subjected to PDT (30 u-g/mt DHE,620–640 nm at 3.94 mW/cnr) and hyperthermia (45.2°C, Haake FK₂ waterbath) for varying lengths of time and sequences. The results show that the two modalities interact in a manner which is more cytotoxic than the sum of the individual treatments, and the sequence of administration is a determining factor in the degree of interaction. The greatest potentiation of PDT is seen when hyperthermia is administered immediately after PDT. Introducing a time interval at 37°C, between treatments, leads to a rapid loss of interaction. Analysis of dose-response curves reveals a return of the shoulder and an increase in the D., after various incubation periods at 37°C. These data suggest that the cells accumulate and demonstrate recovery from sub-lethal damage and also develop a tolerance to a second challenge. The appearance of stress proteins was also detected after PDT treatments, which may account for some of the phenomena observed.