title: DNA methylation changes in cells regrowing after fractioned ionizing radiation.
abstract: OBJECTIVE
  Repeated exposure to ionizing radiation (IR) can result in adaptive reactions. While DNA methylation changes in adaption to repeated stress exposure are established for a variety of drugs, their role in fractioned ionizing radiation is largely unknown.
  
  
  METHODS
  MCF7 breast cancer cells were treated 5 times a week with IR in fractions of 2 Gy, resulting in total doses of 10 and 20 Gy. Cells were harvested 48 and 72 h after the last irradiation, as well as after a recovery period of at least 14 d. To identify genes differentially methylated in irradiated versus non-irradiated cells, we used methyl-CpG immunoprecipitation (MCIp) followed by global methylation profiling on CpG island microarrays.
  
  
  RESULTS
  MCIp profiling revealed methylation changes in several CpG islands 48 h after FIR with 10 and 20 Gy. Cells receiving a total dose of 10 Gy started regrowing after 14 d and exhibited similar radioresistance as mock-treated cells. Differential methylation of the CpG units associated with FOXC1 (p<0.001) and TRAPPC9 (p<0.001) could be confirmed by time-of-flight mass spectrometry (Sequenom).
  
  
  CONCLUSIONS
  In summary, these data indicate that regrowth of MCF7 cells after 10 Gy FIR is associated with locus-specific alterations in DNA methylation.
authors.affiliation: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Kuhmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Weichenhan
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Peter
authors.initials: P
authors.lastname: Schmezer
authors.forename: Odilia
authors.initials: O
authors.lastname: Popanda
mesh_terms: D000222:Adaptation, Physiological; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000528:radiation effects*; D018899:CpG Islands / Q000528:radiation effects; D019175:DNA Methylation; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D047468:Immunoprecipitation; D046228:Microarray Analysis; D011839:Radiation, Ionizing; D012016:Reference Values; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured