Singlet oxygen intermediacy in the photodynamic action of membrane-bound hematoporphyrin derivative.

The cell-damaging photochemistry of hematoporphyrin derivative (HPD) has been investigated using isolated erythrocyte membranes as a test system. Irradiation of membranes in the presence of the tumor-localizing fraction of HPD resulted in formation of singlet molecular oxygen (1O2) as measured by the phosphorescence at 1268 nm. The authentic product of 1O2 attack on cholesterol, 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide, was identified in this system. Relatively insignificant amounts of free radical-derived hydroperoxides were detected. These results suggest that 1O2 plays a major role in the HPD-sensitized photokilling of tumor cells in vivo.