Vol. 173, No. 1,1990 November 30,1990 BIOCHEMICAL AND BIOPHYSICALRESEARCH COMMUNICATIONS Pages 34-41 EVIDENCE FOR THE INVOLVEMENT OF SINGLET OXYGEN IN THE PHOTODESTRUCTION BY CHLOROALUMINUM PHTHALOCYANINE TETRASULFONATE RAJESH AGARWAL, MOHAMMAD ATHAR, DAVID R. BICKERS, and HASANMUKHTAR Department of Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, and Veterans Affairs Medical Center, Cleveland, OH 44106 Received October 12, 1990 In recent years, chloroaluminum phthalocyanine tetrasulfonate (AIPCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, AIPCTS is going to be under clinical trials of PDT. In this study, in vitro addition of AIPCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (-675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of AIPCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, ~-carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the AiPCTS-mediated photodestructive process. © 1990 Academic Press, Inc. The use of photosensitizing chemicals combined with light is known as photodynamic therapy (PDT) and affords the potential for targeted destruction of malignant neoplasms (i). Porphyrin derivatives, the major class of chemicals that have been studied in this regard (2,3), unfortunately possess several intrinsic disadvantages (4,5). This has led to the search for new photosen- sitizers with an improved therapeutic ratio. Chloroaluminum phthalocyanine tetrasulfonate (AIPCTS) has shown promise in this regard. It is non-toxic even at high doses in several mammalian species (6-9), and when injected to animals, has a relatively short retention time in tissues including normal skin (5,10). AIPCTS has been shown to preferentially localize in tumor tissues and on exposure to red light (600-700 nm) results in tissue necrosis (7,8,11-13). Clinical trials using AIPCTS in PDT are about to start in Israel (14), however the exact mechanism of tumor ablation and cutaneous photosensitization associated with this photosensi- tizer remain undefined. 0006-29l X/90 $1.50 Copyright © 1990 by Academic Press, Inc. All rights of reproduction in any form reserved. 34