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

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

Author information

1
Health Protection Agency-Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire, UK. jackie.haines@hpa.org.uk

Abstract

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.

PMID:
20545567
DOI:
10.3109/09553001003734600
[Indexed for MEDLINE]

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