Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

Journal Article · Tue Feb 01 00:00:00 EST 2011 · Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis, 707(1-2):24-33

DOI:https://doi.org/10.1016/j.mrfmmm.2010.12.003· OSTI ID:1009701

Aypar, Umut; Morgan, William F; Baulch, Janet E

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1009701
• Report Number(s): PNNL-SA-76028; KP1602020; TRN: US201107%%815
• Journal Information: Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis, 707(1-2):24-33, Vol. 707, Issue 1-2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
CELL KILLING
CHROMATIN
DNA
DNA DAMAGES
GENES
HYPOTHESIS
INDUCTION
INSTABILITY
IRON
IRRADIATION
LET
LUNGS
METHYLATION
NEOPLASMS
PROMOTERS
RADIATIONS
Ionizing radiation
X-rays
Fe ions
Epigenetics
methylation
MicroRNA
NF-KAPPA-B
INDUCED GENOMIC INSTABILITY
HAMSTER PANCREATIC TUMORS
ABERRANT DNA METHYLATION
NON-CPG METHYLATION
OXIDATIVE STRESS
CHROMOSOMAL INSTABILITY
PROMOTER METHYLATION
EPITHELIAL-CELLS
TSLC1 GENE