title: Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes.
abstract: OBJECTIVE
  It has been shown that exposure to extremely-low frequency (˂300Hz) oscillating electromagnetic field (EMF) can affect gene expression. The effects of different exposure patterns of 50-Hz EMF and co-treatment of EMF plus cisplatin (CDDP) on mRNA levels of seven genes involved in DNA repair pathways (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) were evaluated.
  
  
  METHODS
  Two 50-Hz EMF intensities (0.25 and 0.50mT), three exposure patterns (5min field-on/5min field-off, 15min field-on/15min field-off, 30min field-on continuously) and two cell lines (MCF-7 and SH-SY5Y) were used. The mRNA levels were measured using quantitative real-time PCR.
  
  
  RESULTS
  The examined genes had tendency to be down-regulated in MCF-7 cells treated with EMF. In the pattern of 15min field-on/15min field-off of the 0.50mT EMF, no increase in mRNA levels were observed, but the mRNA levels of GADD45A, XRCC1, XRCC4, Ku80, Ku70, and LIG4 were down-regulated. A significant elevation in IC50of CDDP was observed when MCF-7 and SH-SY5Y cells were co-treated with CDDP+EMF in comparison with the cells treated with CDDP alone. GADD45A mRNA levels in MCF-7 and SH-SY5Y cells co-treated with CDDP+EMF were increased and at the same time the mRNA levels of XRCC4, Ku80, Ku70 and DNA-PKcs were down-regulated.
  
  
  CONCLUSIONS
  Present study provides evidence that co-treatment of CDDP+EMF can enhance down-regulation of the genes involved in non-homologous end-joining pathway. It might be suggested that co-treatment of CDDP+EMF could be more promising for sensitizing cancer cells to DNA double strand breaks.
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran. Electronic address: fsanie@shirazu.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sanie-Jahromi
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran. Electronic address: isaadat@shirazu.ac.ir.
authors.forename: Iraj
authors.initials: I
authors.lastname: Saadat
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran. Electronic address: saadat@shirazu.ac.ir.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Saadat
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D059766:DNA End-Joining Repair / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004574:Electromagnetic Fields; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects; D000097642:GADD45 Proteins
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002945:Cisplatin; D009687:Nuclear Proteins; D012333:RNA, Messenger; C439070:GADD45A protein, human; D000097642:GADD45 Proteins
keywords: BER; Cisplatin; Electromagnetic field; Gene expression; NER; NHEJ