scholarly journals The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation

Author(s):  
Qiong Wang ◽  
Yangyang Chen ◽  
Haiyan Chang ◽  
Ting Hu ◽  
Jue Wang ◽  
...  

Objective: This study aimed to investigate the effect of ataxia telangiectasia mutated (ATM)–mediated autophagy on the radiosensitivity of lung cancer cells under low-dose radiation and to further investigate the role of ATM and its specific mechanism in the transition from hyper-radiosensitivity (HRS) to induced radioresistance (IRR).Methods: The changes in the HRS/IRR phenomenon in A549 and H460 cells were verified by colony formation assay. Changes to ATM phosphorylation and cell autophagy in A549 and H460 cells under different low doses of radiation were examined by western blot, polymerase chain reaction (PCR), and electron microscopy. ATM expression was knocked down by short interfering RNA (siRNA) transfection, and ATM-regulated molecules related to autophagy pathways were screened by transcriptome sequencing analysis. The detection results were verified by PCR and western blot. The differential metabolites were screened by transcriptome sequencing and verified by colony formation assay and western blot. The nude mouse xenograft model was used to verify the results of the cell experiments.Results: (1) A549 cells with high expression of ATM showed positive HRS/IRR, whereas H460 cells with low expression of ATM showed negative HRS/IRR. After the expression of ATM decreased, the HRS phenomenon in A549 cells increased, and the radiosensitivity of H460 cells also increased. This phenomenon was associated with the increase in the autophagy-related molecules phosphorylated c-Jun N-terminal kinase (p-JNK) and autophagy/Beclin 1 regulator 1 (AMBRA1). (2) DL-Norvaline, a product of carbon metabolism in cells, inhibited autophagy in A549 cells under low-dose radiation. DL-Norvaline increased the expression levels of ATM, JNK, and AMBRA1 in A549 cells. (3) Mouse experiments confirmed the regulatory role of ATM in autophagy and metabolism and its function in HRS/IRR.Conclusion: ATM may influence autophagy through p-JNK and AMBRA1 to participate in the regulation of the HRS/IRR phenomenon. Autophagy interacts with the cellular carbon metabolite DL-Norvaline to participate in regulating the low-dose radiosensitivity of cells.

2018 ◽  
Vol 7 (4) ◽  
pp. 1338-1348 ◽  
Author(s):  
Lei Zhou ◽  
Xiaoying Zhang ◽  
Hui Li ◽  
Chao Niu ◽  
Dehai Yu ◽  
...  

2002 ◽  
Vol 21 (2) ◽  
pp. 85-90 ◽  
Author(s):  
L E Feinendegen

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.


2017 ◽  
Author(s):  
Huriye Senay KIZILTAN ◽  
Alpaslan MAYADAGLI ◽  
Ali Hikmet ERIS ◽  
Ozgur KABLAN ◽  
Sezgi Turan EROGUZ ◽  
...  

Author(s):  
Hamid Ghaznavi ◽  
Farideh Elahimanesh ◽  
Jamil Abdolmohammadi ◽  
Meysam Mirzaie ◽  
Sadegh Ghaderi

Abstract Background: The Coronavirus disease 2019 (COVID-19) is spreading rapidly throughout the world. Lung is the primary organ which the COVID-19 virus affects and leads to pneumonia, an acute respiratory distress syndrome. COVID-19 infects the lower respiratory system, and the lung’s response to this infection is recruiting macrophages and monocytes leading to inflammation, this response causes widespread damage to the lung’s airways. Aim: The purpose of this study is to review studies of using low-dose radiation as a treatment for the inflammation of the tissue and pneumonia resulting from COVID-19. These studies were compared with the risk of developing lung cancer during performed dose for the treatment of COVID-19 in radiation therapy. Materials and methods: Our study focused on in vitro, in vivo and clinical reports of using low-dose radiation for the treatment of inflammation, pneumonia and COVID-19. The risk of lung cancer resulting from suggested dose in these studies was also evaluated. Conclusion: From the review of articles, we have found that low-dose radiation can lead to improvement in inflammation in different line cells and animals; in addition, it has been effective in treating inflammation and pneumonia caused by COVID-19 in human up to 80%. Since suggested doses do not remarkably increase the lung cancer risk, low-dose radiation can be an adjuvant treatment for COVID-19 patients.


2010 ◽  
Vol 94 ◽  
pp. S41-S42
Author(s):  
H. Keller ◽  
D. Vines ◽  
M. Lakshman ◽  
M. Dunne ◽  
P. Lindsay ◽  
...  

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110399
Author(s):  
Xiao-Chun Wang ◽  
Li-Li Tian ◽  
Cai-Xia Fan ◽  
Cai-Hong Duo ◽  
Ke-Ming Xu

Objective To study the effects of adaptive response in A549 cells induced by low-dose radiation and the miRNAs expression. Methods A549 cells were irradiated with 50 mGy and 200 mGy initial doses, respectively, and then irradiated with a challenge dose 20 Gy at 6 hours interval. The biological effects and miRNA expression were detected. Results The apoptosis rates of 50 mGy-20 Gy and 200 mGy-20 Gy groups were significantly lower than that of only 20 Gy irradiation group ( P < .05). The percentage of G2/M phase cells of 50 mGy-20 Gy and 200 mGy-20 Gy groups was significantly decreased relative to the 20 Gy group ( P < .05). One miRNA (mir-3662) was upregulated and 15 miRNAs (mir-185, mir-1908, mir-307, mir-182, mir-92a, mir-582, mi-r501, mir138-5p, mir-1260, mir-484, mir-378d, mir-193b, mir-127-3p, mir-1303, and mir-654-5p) were downregulated both in 50 mGy-20 Gy and 200 mGy-20 Gy groups than that of the 20 Gy group. Go and KEGG enrichment analysis showed that the target genes were significantly enriched in cell communication regulation, metabolic process, enzyme binding, and catalytic activity signaling pathways. Conclusion Low-dose X-ray of 50 mGy and 200 mGy radiation can induce adaptive apoptosis response prior to 20 Gy in A549 cells. Sixteen differently expressed miRNAs may play important roles in the adaptive effect of low-dose radiation.


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