title: Radiation-induced epigenetic DNA methylation modification of radiation-response pathways.
abstract: DNA methylation can regulate gene expression and has been shown to modulate cancer cell biology and chemotherapy resistance. Therapeutic radiation results in a biological response to counter the subsequent DNA damage and genomic stress in order to avoid cell death. In this study, we analyzed DNA methylation changes at>450,000 loci to determine a potential epigenetic response to ionizing radiation in MDA-MB-231 cells. Cells were irradiated at 2 and 6 Gy and analyzed at 7 time points from 1-72 h. Significantly differentially methylated genes were enriched in gene ontology categories relating to cell cycle, DNA repair, and apoptosis pathways. The degree of differential methylation of these pathways varied with radiation dose and time post-irradiation in a manner consistent with classical biological responses to radiation. A cell cycle arrest was observed 24 h post-irradiation and DNA damage, as measured by γH2AX, resolved at 24 h. In addition, cells showed low levels of apoptosis 2-48 h post-6 Gy and cellular senescence became significant at 72 h post-irradiation. These DNA methylation changes suggest an epigenetic role in the cellular response to radiation.
authors.affiliation: Department of Radiation Oncology; Wayne State University and Karmanos Cancer Institute; Detroit, MI USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Antwih
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Gabbara
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Lancaster
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Ruden
authors.forename: Steven P
authors.initials: SP
authors.lastname: Zielske
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D019175:DNA Methylation / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D044127:Epigenesis, Genetic; D063990:Gene Ontology; D006801:Humans; D011836:Radiation Tolerance; D013997:Time Factors
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: 5-methylcytosine; DNA methylation; DNA repair; apoptosis; cell cycle; epigenetics; gene ontology; profiling; radiation