THE PHOTOBIOLOGY OF PHOTODYNAMIC THERAPY - CELLULAR TARGETS AND MECHANISMS

Photodynamic therapy (PDT) is dependent on the uptake of a photosensit izing dye, often a porphyrin-related macrocycle, by the tumor or other abnormal tissue that is to be treated, the subsequent irradiation of the tumor with visible light of an appropriate wavelength matched to t he absorption spectrum of the dye, and molecular oxygen to generate re active oxygen intermediates. The initial oxidative reactions lead to d amage to organelles in which the dye is bound, culminating in cell dea th and destruction of the tumor or abnormal tissue. Apoptosis is a com mon mechanism of cell death after PDT both in vitro and in vivo. PDT a lso triggers the activation of several signal transduction pathways in the treated cells; some of these are stress responses aimed at cell p rotection, while others are likely to contribute to the cell death pro cess. The photosensitizers of greatest interest in PDT bind to various cytoplasmic membranes but are not found in the nucleus and do not bin d to DNA. Nevertheless, some DNA damage is produced that can lead to m utagenesis, the extent of which is dependent on the photosensitizer, t he cellular repair properties and the target gene. Thus, in spite of g enerating some responses common to ionizing radiation and other oxidat ive stresses, PDT is unique in the subcellular localization of damage, the combination of signaling pathways that are activated, and rapid k inetics of the induction of cell death processes. (C) 1998 by Radiatio n Research Society.