title: Role of DNA methylation in long-term low-dose γ-rays induced adaptive response in human B lymphoblast cells.
abstract: OBJECTIVE
  With widespread use of ionizing radiation, more attention has been attracted to low-dose radiation (LDR); however, the mechanisms of long-term LDR-induced bio-effects are unclear. Here, we applied human B lymphoblast cell line HMy2.CIR to monitor the effects of long-term LDR and the potential involvement of DNA methylation.
  
  
  METHODS
  HMy2.CIR cells were irradiated with 0.032 Gy γ-rays three times per week for 1-4 weeks. Some of these primed cells were further challenged with 2 Gy γ-rays. Cell proliferation, micronuclei formation, gene expression of DNA methyltransferases (DNMT), levels of global genomic DNA methylation and protein expression of methyl CpG binding protein 2 (MeCP2) and heterochromatin protein-1 (HP1) were measured.
  
  
  RESULTS
  Long-term LDR enhanced cell proliferation and clonogenicity and triggered a cellular adaptive response (AR). Furthermore, global genomic DNA methylation was increased in HMy2.CIR cells after long-term LDR, accompanied with an increase of gene expression of DNMT1 and protein expression of MeCP2 and HP1. After treatment with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, the long-term LDR-induced global genomic DNA hypermethylation was decreased and the AR was eliminated.
  
  
  CONCLUSIONS
  Global genomic DNA hypermethylation accompanied with increases of DNMT1 and MeCP2 expression and heterochromatin formation might be involved in long-term LDR-induced adaptive response.
authors.affiliation: Institute of Radiation Medicine, Fudan University , Shanghai , P. R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ye
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000528:radiation effects*; D000077209:Decitabine; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006570:Heterochromatin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects
chemical_list: D006570:Heterochromatin; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine