Dose- and time-dependence of radiation-induced nitric oxide formation in mice as quantified with electron paramagnetic resonance.

In vivo nitric oxide (NO) formation was quantified in mice after exposure to high-dose whole-body X-ray irradiation. NO produced and accumulated in the livers of irradiated mice was determined using NO trapping method with iron-dithiocarbamate complex combined with electron paramagnetic resonance (EPR) spectroscopy. When mice were irradiated with 50 Gy X-ray, NO formation peaked in approximately 3 h after the irradiation was terminated. Dose-dependence study indicated that NO formation measured 5 h after irradiation was leveled off at the dose higher than 50 Gy. Administration of NO synthase inhibitor, N(G)-monomethyl L-arginine (L-NMMA) shortly after irradiation completely abolished the NO signal, indicating that radiation-induced NO is produced through L-arginine-dependent NO synthase pathways. These results suggest that irradiation of X-ray initiates inflammation processes, resulting in delayed NO synthase expression and NO formation.