The Importance of Singlet Delta Oxygen in Cancer Photoradiation Therapy

A recently developed method of cancer treatment known as photo radiation therapy] or, synonymously, as photochemotherapy involves the combined effects of an intravenously injected hematoporphyrin derivative dye and subsequent irradiation of the diseased area with visible light in the presence of dissolved oxygen. This therapy has been particularly effective in the treatment of early-stage lung cancer. 2 Hematoporphyrin derivative is a mixture of compounds obtained by reacting hematoporphyrin with acetic acid in the presence of sulfuric acid. Hematoporphyrin, in turn, is obtained from the hemoglobin of natural blood. Light interacting with the hematoporphyrin derivative causes it to be excited from its ground singlet state to a metastable triplet state with a lifetime of a few millionths of a second during which it is capable of rapidly energizing dissolved oxygen to its first excited electronic state. This energetic and reactive state of oxygen, lying one electron volt above its ground triplet state (corresponding to a temperature equivalent of 10,000 K), is also shortlived but very reactive. Oxygen in this state is referred to as singlet delta molecular oxygen; it is designated symbolically as ] O 2 to differentiate it from the conventional, stable, ground triplet state species 3 O 2 • The effectiveness of ] O2 in biological systems stems from its reactive oxidative behavior. It has been shown to produce physical rupture of cell membranes, to impair membrane transport functions, to inactivate internal organelles such as mitochondria, and to a lesser degree to induce DNA strand scission. Since the lifetime of ] O2 in cellular media is short (a few microseconds in the ·surrounding and internal watery phase of a cell and tens of microseconds in such fatty (lipid) environments as the cell membrane), it is clear that, in order to be effective in cell destruction, ] O 2 must be generated close to the vulnerable target it is intended to destroy. In water, for example, the distance through which] O2 is capable of diffusing during its lifetime is of the order of 10 5 centimeters, which is small compared with the diame-