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Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts
Marilyn N Vera-Chang1, John M Danforth2, Marilyne Stuart3
1Radiobiology and Health Branch, Chalk River Laboratories, Canadian Nuclear Laboratories, Chalk River, ON, K0J 1J0, Canada.
Clinical Epigenetics
|October 27, 2023
Summary
Alpha (α) radiation exposure alters DNA methylation in lung cells, with single exposures decreasing methylation and multiple exposures increasing it. These changes impact aging and cancer genes, suggesting adaptive responses to radiation.
Area of Science:
- Environmental epigenetics
- Radiation biology
- Genomics
Background:
- Alpha (α)-radiation is an environmental agent with epigenotoxic effects.
- Human exposure to α-radiation can occur via radon inhalation or nuclear accidents.
- DNA methylation (DNAm) alterations are linked to aging and cancer, but their role in α-irradiated lung cells is unknown.
Purpose of the Study:
- To investigate the effects of single-fraction (SF) and multi-fraction (MF) α-irradiation on the DNA methylome of human lung fibroblasts.
- To identify potential DNAm biomarkers associated with α-radiation exposure.
Main Methods:
- Genome-wide DNAm profiling of human embryonic lung fibroblasts exposed to americium-241 α-sources.
- Utilized SF and MF exposure regimens at seven different doses.
- Analyzed differentially methylated regions in gene bodies, oncogenes, tumor suppressor genes, and mitochondria dysfunction-related genes.
Main Results:
- SF α-irradiation decreased DNAm levels, while MF irradiation increased DNAm.
- Gene bodies (exons and introns) were the most affected regions by both SF and MF irradiation.
- MF irradiation induced more differentially methylated regions in genes linked to aging, cancer, and cardiovascular disease.
- MF irradiation also affected genes related to mitochondrial dysfunction, suggesting adaptive mechanisms.
Conclusions:
- Lung cell methylome response to α-radiation depends on dose and exposure regimen (SF vs. MF).
- Findings reveal contrasting methylomic profiles for SF and MF exposures.
- Identified potential α-radiation biomarkers for disease detection, prevention, and treatment.
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