Sensitization of photohemolysis by hypericin and Photofrin

Sensitization of post-irradiation (delayed) photohemolysis (DPH) and "during irradiation" (continuous) photohemolysis (CPH) were investigated for sodium hypericin and Photofrin. The photohemolysis rate and relative steepness of the photohemolysis curves were measured for a range of sensitizer concentrations and DPH irradiation times. The data are analyzed by a multihit model based on the assumption that photohemolysis requires thermal activation of light-activated damage. A key result of the model is the photohemolysis rate has a power dependence of 1 or more on the irradiation time and sensitizer concentration for DPH and a power dependence of less than 1 on sensitizer concentration for CPH. The data for sodium hypericin are consistent with the predictions and indicative of a square dependence of photohemolysis rate on the absorbed light dose. The results for Photofrin led to an approximately square dependence of the photohemolysis rate on DPH irradiation time and an apparently anomalous 1.24 power dependence on sensitizer concentration. The model predicts also that the relative steepness of the photohemolysis curves is independent of the light dose and sensitizer concentration for DPH and almost independent of the sensitizer concentration for CPH. This prediction is confirmed to within +/- 10% for all sets of DPH and CPH curves. The relationship of the multihit kinetics model to detailed photohemolysis mechanisms is discussed.