Low-dose radiation induced modification of ROS and apoptosis in thymocytes of whole body irradiated mice

Abstract

Whole body irradiation (WBI) to a single dose of 3 Gy of γ-rays has earlier been shown in our laboratory to induce thymic lymphoma (TL) after 4-5 months in Swiss mice. The tumour induction was significantly found suppressed when animals were pre-exposed to radiation doses in the range of a few cGy. Recent research efforts have been focused to investigate the molecular mechanism of these observations. In vitro studies on thymocytes from irradiated mice have shown a radiation dose (1-5 Gy) and post-irradiation (3 Gy) time dependent increase in intracellular reactive oxygen species (ROS) as measured by 2,7-dichlorodihydroflurescein diacetate (DCH-FDA) and enhanced apoptosis as measured by fluorescent probe, merocyanine-540 (MC-540). Typically, a five-fold increase in ROS and apoptosis was observed in thymocytes collected 30 minutes after exposure of mice to a dose of 5 Gy suggesting substantial up-regulation of ROS in cells after exposure of animal to moderate oxidative stress. It was further found that increased cellular ROS was correlated with induction of apoptosis in thymocytes of irradiated mice. Pre-exposure of animals with 1 cGy was found to significantly inhibit ROS generation and apoptosis induction in thymocytes from whole body irradiated (3 Gy) mice suggesting suppressive effect of low dose irradiation. Moreover, exposure of animals with fractionated low doses of 1 × 1, 3 × 1 and 5 × 1 cGy yielded increasing level of ROS in cells suggesting dose-dependent accumulative radiation damage. These results would have significant implications in understanding the mechanism of low dose induced suppression in tumour induction by radiation.