IDH1(R132H) mutation increases U87 glioma cell sensitivity to radiation therapy in hypoxia

Biomed Res Int. 2014:2014:198697. doi: 10.1155/2014/198697. Epub 2014 May 7.

Abstract

Objective: IDH1 codon 132 mutation (mostly Arg132His) is frequently found in gliomas and is associated with longer survival. However, it is still unclear whether IDH1 mutation renders the cell more vulnerable to current treatment, radio- and chemotherapy.

Materials and methods: We transduced U87 with wild type IDH1 or IDH1 (R132H) expressing lentivirus and analyzed the radiosensitivity (dose ranging 0 to 10 Gy) under normoxia (20% O2) and moderate hypoxia (1% O2).

Results: We observed that IDH1 (R132H) U87 cells grow faster in hypoxia and were more sensitive to radiotherapy (in terms of cell mortality and colony formation assay) compared to nontransduced U87 and IDH1 (wt) cells. This effect was not observed in normoxia.

Conclusion: These data suggest that IDH1 (R132H) mutation increases radiosensitivity in mild hypoxic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / radiotherapy*
  • Cell Hypoxia / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / radiation effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Glioma / enzymology
  • Glioma / genetics
  • Glioma / pathology*
  • Glioma / radiotherapy*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Mutation / genetics*
  • Radiation Tolerance / radiation effects*
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Time Factors
  • Transduction, Genetic
  • Tumor Stem Cell Assay

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human