title: Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality.
abstract: OBJECTIVE
  To investigate microsatellite instability (MSI) in radiation-induced murine tumours, its dependence on tissue (haemopoietic, intestinal, mammary, brain and skin) and radiation type.
  
  
  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.
authors.affiliation: Health Protection Agency-Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire, UK. jackie.haines@hpa.org.uk
authors.forename: Jackie
authors.initials: J
authors.lastname: Haines
authors.forename: Jeff
authors.initials: J
authors.lastname: Bacher
authors.forename: Margaret
authors.initials: M
authors.lastname: Coster
authors.forename: Rene
authors.initials: R
authors.lastname: Huiskamp
authors.forename: Emmy
authors.initials: E
authors.lastname: Meijne
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Simon
authors.initials: S
authors.lastname: Bouffler
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism / Q000528:radiation effects; D019075:Electrophoresis, Capillary; D005347:Fibroblasts / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053842:Microsatellite Instability / Q000528:radiation effects*; D018895:Microsatellite Repeats / Q000528:radiation effects*; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000145:classification / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D009502:Neutrons / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D004247:DNA; D051718:MutS Homolog 2 Protein