Abstract
[Objective] Reoxygenation of hypoxic region in tumor has been widely recognized as a typical response of tumor tissue toward ionizing radiation. However, the mechanism of the radiation-induced tumor reoxygenation has not been fully elucidated. Therefore, we aimed in this study to evaluate the fluctuations in tumor oxygenation status after ionizing radiation and determine the factors responsible for radiation-induced tumor reoxygenation.
[Methods] As an animal model, we used a transplanted tumor of murine squamous carcinoma SCCVII cells in C3H mice. To detect histological change of hypoxic region after X-irradiation, we performed immunohistochemical (IHC) analysis with two different hypoxia probes (pimonidazole and EF5). To examine the change in partial pressure of oxygen (pO2) in tumor, in vivo electron spin resonance (ESR) technique with LiNc-BuO as an oxygen sensitive probe was utilized. To investigate the involvement of nitric oxide (NO˙) in radiation-induced tumor reoxygenation, we tested the effect of a nitric oxide synthase inhibitor, L-NAME.
[Results] Double-stained images of hypoxia revealed that primarily existing hypoxic regions were completely diminished at 24 h after X-irradiation, followed by the recovery at 48 h. The result of ESR oxymetry showed that tumor pO2 was time-dependently increased and peaked at 24 h after X-irradiation, and then decreased and kept at higher level than the pre-irradiation up to 120 h. Administration of L-NAME inhibited the first phase of reoxygenation. These results indicated that X-irradiation induced two-phase reoxygenation and NO˙ was suggested to be involved in the first phase of this reoxygenation.
