Early antioxidant responses via the concerted activation of NF-κB and Nrf2 characterize the gamma-radiation-induced adaptive response in quiescent human peripheral blood mononuclear cells

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis Vol. 831; pp. 50 - 61
• Main Authors: Paraswani, Neha, Thoh, Maikho, Bhilwade, Hari N., Ghosh, Anu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2018
• Subjects: Adult; Antioxidant enzymes; Antioxidants - pharmacology; Catalase; DNA Damage; DNA strand breaks; Gamma Rays; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; Glutathione Peroxidase - metabolism; Healthy Volunteers; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - radiation effects; Low-dose radiation; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidation-Reduction; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; Reactive Oxygen Species - metabolism; ROS; Superoxide Dismutase - metabolism; Young Adult; Low-dose radiation; Antioxidant enzymes; DNA strand breaks; ROS
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2018.04.007

•Pre-exposure to γ-radiation attenuated DNA strand breaks in quiescent human PBMCs.•Primed PBMCs exhibited decreased oxidative stress and increased anti-oxidant responses.•Pre-exposure to γ-radiation increased DNA binding of NF-κB and Nrf2.•γ-radiation of 100 mGy effected an upregulation of CAT and MnSOD activity in PBMCs. The radiation-induced adaptive response (RI-AR) is a non-targeted effect which is outside the scope of the classical Linear-No-Threshold (LNT) dose-response paradigm. However, the mechanisms of the RI-AR are not well understood. We have studied the RI-AR in quiescent human peripheral blood mononuclear cells (PBMCs). PBMCs in G0 phase were ‘primed’ with a low dose (100 mGy gamma radiation) and then, after an ‘adaptive window’ of 4 h, ‘challenged’ with a high dose (2 Gy). A small (5.7%) increase in viability and a decrease in DNA strand breaks were seen in primed cells, compared to non-primed cells. This was consistent with lower levels of reactive oxygen species, higher mitochondrial membrane potential, and increased activity of antioxidant enzymes such as catalase, superoxide dismutase, thioredoxin reductase, and glutathione peroxidase, in the primed cells. Reduced oxidative stress in primed PBMCs correlated with greater nuclear translocation of the redox-sensitive transcription factors Nuclear factor kappa B (NF-κB) and Nuclear factor E2-related factor 2 (Nrf2). Distinct differences in responses were seen in PBMCs irradiated with low dose (100 mGy) and high dose (2 Gy). These findings provide insight into the mechanisms of radioadaptation in human cells.