This assumption is further supported by a very re cent report indicating that ROS comprises a regulator of adhesion molecules very late antigen 4 and vas cular cell adhesion molecule 1 mediated monocytemacrophage adhesion to EC following irradi ation with a dose of 0. 5 Gy. In conclusion our data implicate a non linear regula tion of SOD activity and ROS production in EC follow ing Ganetespib cancer irradiation with doses 1 Gy that may contribute to a discontinuous dose response relationship of phospho histone H2AX detection and a putative discontinuous behaviour of DNA damage response. A mechanistic in volvement of DNA damage repair mechanisms in the modulation of these non linear dose response effects re mains to be established.

However, one may assume that a discontinuous detection of residual H2AX foci in our investigation is related to the phenomenon of low dose hyper radiosensitivity Inhibitors,Modulators,Libraries and induced radioresistance, which have been reported for cellular survival at doses below 0. 3 Gy and in the dose range of 0. 3 Gy to 0. 6 Gy, respectively. In this regard, accumulating ev idences exist on a reduced non homologous end joining repair response associated with HRS and persist ent RAD51 foci, an essential component of the homolo gous recombination pathway at late time points after low dose exposure. This may indicate that a deregulation of both repair pathways Inhibitors,Modulators,Libraries may contribute to the non linear induction of DSBs. Moreover, future in vestigations will further address a putative involvement of accumulation of DSBs at stalled replication forks to contribute to the detection of residual H2AX follow ing a low dose exposure especially in S phase cells.

Introduction Ionizing radiation deposits energy Inhibitors,Modulators,Libraries as single ionizations or as ionization clusters that generate base and sugar da mages in the DNA. Clusters of ionization can gener ate clusters of DNA damage with different sizes and diverse damage composition. Sugar damage can Inhibitors,Modulators,Libraries disrupt the sugar phosphate backbone to gen erate DNA single strand breaks. SSBs within CDSs form DNA double strand breaks, which can have severe biological consequences. DSBs can also be generated from CDSs populated with base damages through bi stranded enzymatic opening during repair of the DNA sugar phosphate backbone, or by combining with a SSB. DSBs initiate rapid signaling and complex regulatory processes affecting Inhibitors,Modulators,Libraries DNA repair, cell cycle progression, transcription, translation, as well as decisions of pro grammed cell death and autophagy.

These responses are currently integrated under the term cellular DNA damage response. Analysis of DDR after IR is based on the assumption that all DSBs form promptly. However, irradiation method of plas mid DNA has shown that IR induces, in addition to sugar lesions promptly disrupting the sugar phosphate backbone, also lesions doing so after temperature dependent chemical processing.