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