Radiation-induced genomic instability in haemopoietic cells

Purpose: To review studies of radiation-induced genomic instability in haem opoietic cells. Major findings: Studies have demonstrated a high frequency of non-clonal, c ytogenetic abnormalities in the clonal descendants of alpha-particle-irradi ated (approximately one track per cell) primary murine and human haemopoiet ic stem cells in vitro. The induction of this phenomenon has a strong depen dence on the genetic characteristics of the cells and is transmissible in v ivo following transplantation of alpha-irradiated mouse bone marrow. In clo nogenic cell cultures of alpha-irradiated haemopoietic cells, there is also an increased incidence of hprt mutations and an increased incidence of apo ptosis. These effects may be regarded as the consequences of a destabilizat ion of the genome collectively termed radiation-induced genomic instability . Instability is induced at very high frequencies suggesting that epigeneti c changes may be a common underlying mechanism. Consistent with this sugges tion is the finding of an enhanced and persisting oxy-radical activity in t he descendants of irradiated stem cells, which is consistent with oxidative stress being an important feature of the mechanism(s) underlying the persi stence of instability in haemopoietic cells. Recent studies have revealed t hat more clonogenic cells than are actually traversed by an alpha-particle are able to express the instability phenotype. These data are consistent wi th unexpected interactions between irradiated and nonirradiated cells but t he mechanism of initiation of instability is not understood.