Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality.
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.
Haines
Jackie
J
Health Protection Agency-Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire, UK. jackie.haines@hpa.org.uk
Bacher
Jeff
J
Coster
Margaret
M
Huiskamp
Rene
R
Meijne
Emmy
E
Mancuso
Mariateresa
M
Pazzaglia
Simonetta
S
Bouffler
Simon
S
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*
D004247:DNA; D051718:MutS Homolog 2 Protein