The apparent production of superoxide and hydroxyl radicals by hematoporphyrin and light as seen by spin-trapping.

Hematoporphyrin is known to have photodynamic properties. The exposure of biomolecules or cells to hematoporphyrin and visible light can result in damage [l] and can even be lethal [2]. This inactivating effect appears to be greater in cancer cells than in corresponding normal cells [3]. This is thought to be due in part to the greater acc~ulation of hematoporphyrin in malignant tissue than in most other tissues 14-71. There is evidence that the cytotoxic action of hematoporphyrin and light is the result of the photosensitized production of singlet oxygen, a short-lived, hi@ly reactive state of molecular oxygen (8-101, However, the interaction of hematoporphyrin with biomolecules may proceed by a radical mechanism rather than by a singlet oxygen mechanism [ 111. In [ 121 evidence indicating the production of hydroxyl radical in cell systems exposed to hematopo~hyr~ and red light appeared. He~topo~hy~ could produce superoxide radical in aprotic solvents 1131, but no free radical formation in the presence of water was observed [ 131. The photosensitized production of superoxide by hematoporphyrin has been reported in [ 141 but only in the presence of NADH or NADPH. Thus, the significance of a radical mechanism for this reaction needs to be thoroughly investigated. In [1.5-l 71 we proposed a new model for malignancy. The essence of the model is as follows: Tumor cells have diminished amounts of the mang~ese~onta~~g superoxide dismuta~, but at the same time they are capable of produc~g significant amounts of superoxide radical. We believe this difference between malignant and normal cells can be exploited in the treatment of cancer. Agents