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 (P0.014) in X-ray-induced tumours and rising again to 83 (P0.001) 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. © 2010 Informa UK Ltd.

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