title: Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling.
abstract: 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.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.|Department of Radiation-Oncology, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Guozi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Dehai
authors.initials: D
authors.lastname: Yu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jifan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Niu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Tian
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Han
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiation-Oncology, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Dong
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.|Kosair Children's Hospital Research Institute, Departments of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000502:physiology*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D019938:Cyclin D1 / Q000032:analysis; D000071679:Glycogen Synthase Kinase 3 beta / Q000502:physiology; D006801:Humans; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C530104:CCND1 protein, human; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D019938:Cyclin D1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: ATM; biological effects; low-dose radiation; lung cancer cells; normal lung cells