Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling
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Guozi Yang1,2,*, Dehai Yu1,*, Wei Li1, Yuguang Zhao1, Xue Wen1, Xinyue Liang1, Xiaoying Zhang1, Lei Zhou1, Jifan Hu1, Chao Niu1, Huimin Tian1, Fujun Han1, Xiao Chen1, Lihua Dong2, Lu Cai1,3, Jiuwei Cui1
1Cancer Center, The First Hospital of Jilin University, Changchun 130021, China
2Department of Radiation-Oncology, The First Hospital of Jilin University, Changchun 130021, China
3Kosair Children’s Hospital Research Institute, Departments of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA
*These authors contributed equally to this work
Jiuwei Cui, email: firstname.lastname@example.org
Lu Cai, email: L0cai001@louisville.edu
Keywords: low-dose radiation, normal lung cells, lung cancer cells, biological effects, ATM
Received: February 03, 2016 Accepted: September 25, 2016 Published: September 30, 2016
Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells but not in cancer cells, suggesting its potential protection of normal tissue against damage induced by conventional radiotherapy. However, the underlying mechanisms are not well established. We addressed this in the present study by examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7 (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the initiating event in hormesis and adaptive response to LDR in HBE cells. ATM activation increased the expression of CDK4/CDK6/cyclin D1 by activating the AKT/glycogen synthase kinase (GSK)-3β signaling pathway, which stimulated HBE cell proliferation. Activation of ATM/AKT/GSK-3β signaling also increased nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to increased expression of antioxidants, which mitigated cellular damage from excessive reactive oxygen species production induced by high-dose radiation. However, these effects were not observed in A549 cells. Thus, the failure to activate these pathways in A549 cells likely explains the difference between normal and cancer cells in terms of hormesis and adaptive response to LDR.
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