Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality

Int J Radiat Biol. 2010 Jul;86(7):555-68. doi: 10.3109/09553001003734600.


Purpose: To investigate microsatellite instability (MSI) in radiation-induced murine tumours, its dependence on tissue (haemopoietic, intestinal, mammary, brain and skin) and radiation type.

Materials and methods: DNA from spontaneous, X-ray or neutron-induced mouse tumours were used in Polymerase Chain Reactions (PCR) with mono- or di-nucleotide repeat markers. Deviations from expected allele size caused by insertion/deletion events were assessed by capillary electrophoresis.

Results: Tumours showing MSI increased from 16% in spontaneously arising tumours to 23% (P = 0.014) in X-ray-induced tumours and rising again to 83% (P << 0.001) in neutron-induced tumours. X-ray-induced Acute Myeloid Leukaemias (AML) had a higher level of mono-nucleotide instability (45%) than di-nucleotide instability (37%). Fifty percent of neutron-induced tumours were classified as MSI-high for mono-nucleotide markers and 10% for di-nucleotide markers. Distribution of MSI varied in the different tumour types and did not appear random.

Conclusions: Exposure to ionising radiation, especially neutrons, promotes the development of MSI in mouse tumours. MSI may therefore play a role in mouse radiation tumourigenesis, particularly following high Linear Energy Transfer (LET) exposures. MSI events, for a comparable panel of genome-wide markers in different tissue types, were not randomly distributed throughout the genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA / isolation & purification
  • DNA / metabolism
  • DNA / radiation effects
  • Electrophoresis, Capillary
  • Fibroblasts / pathology
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microsatellite Instability / radiation effects*
  • Microsatellite Repeats / radiation effects*
  • MutS Homolog 2 Protein / metabolism
  • Neoplasms, Radiation-Induced / classification
  • Neoplasms, Radiation-Induced / etiology*
  • Neoplasms, Radiation-Induced / genetics*
  • Neoplasms, Radiation-Induced / pathology
  • Neutrons / adverse effects*
  • Polymerase Chain Reaction
  • X-Rays / adverse effects*


  • DNA
  • MutS Homolog 2 Protein