Cellular redox status mediates adaptive response to ionizing radiation in human peripheral blood mononuclear cells

Radioadaptive response refers to the phenomenon where a small priming dose of ionizing radiation (IR) reduces the detrimental effects of subsequent higher IR dose. In this study, we demonstrated that adaptive response in human peripheral blood mononuclear cells (PBMCs) is associated with altered cellular oxidative stress. DNA strand breaks, analysed with comet assay and γH2AX, was used as the endpoint to demonstrate adaptive response in PBMCs exposed to a priming dose of 10 cGy Co60 γ-rays followed by a challenge dose of 2 Gy γ-rays (dose rate 0.3 Gy/min) after 4 hours. Primed cells showed significantly lesser DNA damage accompanied with decreased levels of ROS and increased antioxidant responses. This included changes in the expression for genes like SOD2, GPx, CAT and TRX. In addition, increased activity of enzymatic defense system, mainly SOD and TXNRD, but not CAT and GPx, was observed in the primed cells. These responses were shown to be mediated through increased DNA binding of stress responsive transcription factors Nrf2 and NFκB. The primed cells also showed early activation of ERK, p38 and JNK MAP kinases. Label-free LCMS analysis revealed unique pattern of differentially expressed proteins in the primed cells. A better understanding of adaptive response will contribute towards refinement of radiation protection strategies and radiotherapy protocols.