Genetic instability in radiation-induced leukaemias: mouse models

Purpose: Genetic instability plays a major role in multi-stage carcinogenes is. Ionizing radiation induces delayed genetic instability which can be tra nsmitted to the clonal offspring of the irradiated cell, so it is of consid erable importance to determine whether radiation-induced genetic instabilit y contributes to radiation-leukaemogenesis. Results: The experimental data obtained using radiation-induced leukaemias in mouse models were reviewed, and an attempt was made to distinguish betwe en the instability detectable in de novo cancers and that which is associat ed with ionising radiation. Genetic lesions identified in mouse leukaemias include nonclonal chromosomal aberrations, loss of heterozygosity, and mini satellite/microsatellite mutations. Conclusions: Studies of mouse radiation-induced leukaemias have detected ev idence of genetic instability. However, with few exceptions, most of this i nstability was also observed during de novo multi-stage carcinogenesis. Thi s raises the possibility that radiation induces ongoing genetic instability that is Functionally indistinguishable to that implicated in de novo tumou r progression.