Radiation-induced genomic instability in haemopoietic cells

Purpose: To review studies of radiation-induced genomic instability in haemopoietic cells. Major findings: Studies have demonstrated a high frequency of non-clonal, cytogenetic abnormalities in the clonal descendants of alpha-particle-irradiated (approximately one track per cell) primary murine and human haemopoietic stem cells in vitro. The induction of this phenomenon has a strong dependence on the genetic characteristics of the cells and is transmissible in vivo following transplantation of alpha-irradiated mouse bone marrow. In clonogenic cell cultures of alpha-irradiated haemopoietic cells, there is also an increased incidence of hprt mutations and an increased incidence of apoptosis. These effects may be regarded as the consequences of a destabilization of the genome collectively termed radiation-induced genomic instability. Instability is induced at very high frequencies suggesting that epigenetic changes may be a common underlying mechanism. Consistent with this suggestion is the finding of an enhanced and persisting oxy-radical activity in the descendants of irradiated stem cells, which is consistent with oxidative stress being an important feature of the mechanism(s) underlying the persistence of instability in haemopoietic cells. Recent studies have revealed that more clonogenic cells than are actually traversed by an alpha-particle are able to express the instability phenotype. These data are consistent with unexpected interactions between irradiated and nonirradiated cells but the mechanism of initiation of instability is not understood.