The influence of oxygen on the radiosensitizing activity of Photofrin II and hypericin

Several clinical studies, as well as investigations performed on tissue cultures and murine tumor models, have demonstrated the in vitro and in vivo efficacy of Photofrin II and hypericin as radiosensitizing agents. The mechanisms involved in the radiosensitizing action of Photofrin II and hypericin are partially understood; the recognition of the major role performed by oxygen regarding the modulation of cellular radiosensitivity has prompted the present investigations on the relevance of oxygenation for the success of Photofrin II or hypericin-based radiation therapy of tumors. RT4 human bladder carcinoma cell lines were seeded and incubated with various concentrations of Photofrin II or hypericin under ambient and 5% oxygen levels. The cells were irradiated with ionizing radiation between 1 and 6 Gy. The same experiments were repeated with Photofrin II and hypericin alone, without radiation. The cell survival was evaluated. The results demonstrated an increase of radiation-induced cell damage in the presence of Photofrin II and hypericin, respectively, when sufficient oxygen was available. Low levels of oxygen reduced the activity of Photofrin II as well as of hypericin as a radiosensitizer, with minimal tumor damage ( p < 0.05 in a Student t-test). The mechanism of action of Photofrin II and hypericin as radiosensitizers requires the presence of sufficiently high oxygen concentrations.