hy926 EC were irradiated in the presence of the ROS scavenger NAC. In pilot experi ments NAC treatment was proven to result in a significant reduction in total ROS levels to 20% of mock treated controls. As illustrated in Figure 4B, the non linear appearance of H2AX foci was com pletely abolished upon pre treatment with NAC, indicat selleck chemicals llc ing a direct correlation between ROS production and the biphasic behaviour of H2AX detection. Discussion Although considerable progress has been achieved in the understanding of immune modulatory effects of ionising ra diation, the underlying molecular mechanisms are presently not fully resolved. In line with that, high dose exposure with single doses exceeding 2 Gy displays a pronounced pro inflammatory effect whereas irradiation with single doses below 1 Gy experimentally and clinically reveal anti inflammatory Inhibitors,Modulators,Libraries properties.

This may implicate the involvement of complex mechanisms of DNA damage re sponse and immune modulation differentially operating at different dose levels. In that context, EC may comprise ideal targets for modulatory properties of low dose and high dose irradiation exposure due to their crucial role in the regulation of the local inflammatory process Inhibitors,Modulators,Libraries both by their ability to recruit leukocytes to Inhibitors,Modulators,Libraries the site of local inflammation and by expressing a variety of cytokines chemokines essential for the inflammatory cascade. Although recent data imply an involvement of a variety of molecular mechanisms in the anti inflammatory characteristics of EC following low dose irradiation, the impact of ROS production to give rise or contribute to these effects in EC remains elusive.

Here we show a linear dose response relationship for H2AX foci induction at 1 h Inhibitors,Modulators,Libraries and 4 h after irradiation irre spective of stimulation of the cells in a pro Inhibitors,Modulators,Libraries inflammatory manner by adding TNF. This may indicate that induc tion of DSBs and early DNA damage repair at low dose ir radiation, at least in EA. hy926 EC, may not be altered in an inflammatory surrounding characteristic for benign diseases treated clinically with LD RT. Moreover, DNA damage repair response is considered to be linear with dose, which is in agreement with our data on the selleck chem linearity of H2AX induction at early times after irradiation. At later times, however, we observed a discontinuous dose response relationship of residual H2AX foci along with a non linear detection of ROS with elevated levels following a 0. 5 Gy expos ure. This further confirms a close relationship between intracellular ROS and the induction of histone H2AX foci as a marker of DNA damage. In line with that, cellular ROS production is tightly regulated by coordi nated activities of pro oxidant and anti oxidant defence mechanisms.