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Series GSE242767 Query DataSets for GSE242767
Status Public on Oct 09, 2023
Title Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Alpha (α)-radiation is a ubiquitous environmental agent with epigenotoxic effects. Human exposure to α-radiation at potentially harmful levels can occur repetitively over the long term via inhalation of naturally occurring radon gas that accumulates in enclosed spaces, or as a result of a single exposure from a nuclear accident. Alterations in epigenetic DNA methylation (DNAm) have been implicated in normal aging and cancer pathogenesis. Nevertheless, the effects of aberrations in the methylome of human lung cells following exposure to single or multiple α-radiation events on these processes remain unexplored. Here, we performed genome-wide DNAm profiling of human embryonic lung fibroblasts from control and irradiated cells using americium-241 α-sources. Cells were α-irradiated in quadruplicates to seven doses using two exposure regimens, a single-fraction (SF) where the total dose was given at once, and a multi-fraction (MF) method, where the total dose was equally distributed over 14 consecutive days. Our results revealed that SF irradiations were prone to a decrease in methylation levels, while MF irradiations mostly increased methylation. The analysis also showed that the gene body (i.e. exons and introns) was the region mostly altered by both the SF hypomethylation and the MF hypermethylation. Additionally, the MF irradiations induced the highest number of differentially methylated regions in genes associated with DNAm biomarkers of aging, carcinogenesis, and cardiovascular disease. The DNAm profile of the oncogenes and tumour suppressor genes suggested that the fibroblasts elicited a defensive response to the MF α-irradiation. Key DNAm events of ionizing radiation exposure including changes in methyl levels in mitochondria dysfunction-related genes were mainly identified in the MF groups. However, these alterations were under-represented, indicating that the mitochondria undergo adaptive mechanisms, aside from methylation, in response to radiation-induced oxidative stress. In this study, we identified a contrasting methylomic profile in the lung fibroblasts α-irradiated to SF compared with MF exposures. These findings demonstrate that the methylome response of the lung cells to α-radiation is highly dependent on both the total dose and the exposure regimen. They also provide novel insights into potential biomarkers of α-radiation which may lead to the development of innovative approaches to detect, prevent and treat α-particle related diseases.
 
Overall design We first irradiated primary lung fibroblast cells to seven doses of americium-241 α-sources ranging from 2.0 to 2,200 mGy using two exposure regimens, a single-fraction where the total dose was given at once, and a multi-fraction method, where the total dose was equally distributed over 14 consecutive days. The irradiation per dose for each regimen was independently conducted in 4 biological replicates. We then performed Methylated DNA immunoprecipitation (MeDIP) coupled with sequencing.
 
Contributor(s) Vera-Chang MN, Danforth JM, Stuart M, Goodarzi AG, Brand M, Richardson RB
Citation(s) 37891670
BioProject PRJNA1010795
Submission date Sep 08, 2023
Last update date Nov 16, 2023
Contact name Richard B. Richardson
E-mail(s) richard.richardson@cnl.ca
Organization name Canadian Nuclear Laboratories
Department Radiobiology and Health
Street address 286 Plant Rd
City Chalk River
State/province Ontario
ZIP/Postal code K0J 1J0
Country Canada
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (128)
GSM7770174 WI-38 cells, single-fraction, 0mGy, 5mC, rep1
GSM7770175 WI-38 cells, single-fraction, 0mGy, 5mC, rep2
GSM7770176 WI-38 cells, single-fraction, 0mGy, 5mC, rep3

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MINiML formatted family file(s) MINiMLHelp
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Supplementary file Size Download File type/resource
GSE242767_MA2_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MA3_50_U1_meth.RData.gz 2.8 Gb (ftp)(http) RDATA
GSE242767_MA4_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MA5_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MA6_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MA7_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MA8_50_U1_meth.RData.gz 2.8 Gb (ftp)(http) RDATA
GSE242767_MC2_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC3_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC4_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC5_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC6_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC7_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
GSE242767_MC8_50_U1_meth.RData.gz 2.9 Gb (ftp)(http) RDATA
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