Haines Jackie, Bacher Jeff, Coster Margaret, Huiskamp Rene, Meijne Emmy, Mancuso Mariateresa, Pazzaglia Simonetta, Bouffler Simon
Health Protection Agency-Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire, UK.
Int J Radiat Biol. 2010 Jul;86(7):555-68. doi: 10.3109/09553001003734600.
To investigate microsatellite instability (MSI) in radiation-induced murine tumours, its dependence on tissue (haemopoietic, intestinal, mammary, brain and skin) and radiation type.
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.
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.
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.
研究辐射诱导的小鼠肿瘤中的微卫星不稳定性（MSI），及其对组织（造血、肠道、乳腺、脑和皮肤）和辐射类型的依赖性。
将来自自发、X射线或中子诱导的小鼠肿瘤的DNA用于聚合酶链反应（PCR），使用单核苷酸或二核苷酸重复标记。通过毛细管电泳评估由插入/缺失事件引起的与预期等位基因大小的偏差。
显示MSI的肿瘤从自发产生的肿瘤中的16%增加到X射线诱导的肿瘤中的23%（P = 0.014），并再次上升到中子诱导的肿瘤中的83%（P << 0.001）。X射线诱导的急性髓性白血病（AML）的单核苷酸不稳定性水平（45%）高于二核苷酸不稳定性水平（37%）。50%的中子诱导肿瘤对于单核苷酸标记被分类为高MSI，对于二核苷酸标记为10%。MSI的分布在不同肿瘤类型中有所不同，且似乎不是随机的。
暴露于电离辐射，尤其是中子，会促进小鼠肿瘤中MSI的发展。因此，MSI可能在小鼠辐射致癌过程中起作用，特别是在高线性能量传递（LET）暴露之后。对于不同组织类型中一组可比的全基因组标记，MSI事件在整个基因组中并非随机分布。
