Tempol Exerts Radioprotective Effects by Suppressing Radiation-Induced DNA Double-Strand Break Formation

Concerns about radiation exposure following the Fukushima Nuclear Power Plant accident continue to grow, and health risks associated with medical radiation have also become an important issue. Therefore, identifying agents that can mitigate radiation-related health effects is necessary. We focused on the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) and investigated its radioprotective mechanisms. HeLa and TIG-3 cells were irradiated with X-rays, γ-rays, or heavy-ion beams. The effect of tempol on reactive oxygen species (ROS) production was evaluated using fluorescence-activated cell sorting (FACS) analysis. DNA double-strand break (DSB) formation was assessed by γ-H2AX immunofluorescence staining. In mice, γ-H2AX formation in the thymus and duodenum were evaluated after acute or chronic γ-ray exposure. Inflammatory responses were analyzed through macrophage infiltration and TNF mRNA expression, while apoptosis was measured using Annexin V staining. Tempol suppressed ROS production and γ-H2AX foci formation following irradiation. It also reduced γ-H2AX induction in mouse tissues. Activated macrophage infiltration and TNF expression in the duodenum tended to decrease in tempol-treated mice, whereas apoptotic levels showed no significant differences. Notably, tempol more effectively inhibited γ-H2AX formation during chronic irradiation than acute exposure. These findings suggest that tempol mitigates radiation-induced inflammation and reduces DNA damage, supporting its potential as a radioprotective agent.