Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation

We have demonstrated chromosomal instability in the clonal descendants of hemopoietic stem cells after irradiating murine bone marrow with alpha-particles. However, because cells that are irradiated by alpha-particles are defined by a Poisson distribution of individual particle traversals, there is an inevitable proportion of unirradiated cells in the surviving population. The calculated expected proportions of irradiated and nonirradiated cells indicate that the number of clonogenic cells transmitting chromosomal instability is greater than the number expected to be hit and survive. To investigate further this discrepancy, we studied the effects of interposing a grid between the cells and the alpha-particle source so that the surviving population consists predominantly of untraversed stem cells. Comparison with the same irradiation conditions without the grid reveals that the same level of instability is induced. The data confirm that alpha-particles induce chromosomal instability but instability is demonstrated in the progeny of nonirradiated stem cells and must be due to unexpected interactions between irradiated and nonirradiated cells. This untargeted effect has important implications for mechanistic studies of radiation action and for assessment of radiation risk.