Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes

Life Sci. 2016 Dec 1:166:41-45. doi: 10.1016/j.lfs.2016.10.006. Epub 2016 Oct 6.

Abstract

Aims: 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.

Main 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.

Key findings: 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 IC50 of 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.

Significance: 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.

Keywords: BER; Cisplatin; Electromagnetic field; Gene expression; NER; NHEJ.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Breaks, Double-Stranded / drug effects
  • DNA End-Joining Repair / drug effects
  • DNA Repair* / drug effects
  • Down-Regulation / drug effects
  • Electromagnetic Fields*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Nuclear Proteins / genetics
  • RNA, Messenger / genetics*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Cisplatin