Effect of linear energy transfer (LET) on complexity of alpha-particle-induced chromosome aberrations in human CD34+ cells.

Abstract

The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles on chromosome aberration complexity in the absence of significant other track structure differences. To do this we irradiated human haemopoietic stem cells (CD34+) with The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles of various incident LET values (110 - 152 keV/µm, with mean LETs through the cell of 119 – 182 keV/µm) at an equi-fluence of approximately 1 α-particle/cell and assayed for chromosome aberrations by m-FISH. Based on a single harvest time to collect early division mitosis , complex aberrations were observed at comparable frequencies irrespective of incident LET, however when expressed as a proportion of the total exchanges detected, their occurrence was seen to increase with increasing LET. Cycle analysis to predict theoretical DNA double strand break rejoining cycles was also carried out on all complex chromosome aberrations detected. By doing this we found that the majority of complex aberrations are formed in single non-reducible cycles that involve just 2 or 3 different chromosomes and 3 or 4 different breaks. Each non-reducible cycle is suggested to represent ‘an area’ of finite size within the nucleus where double strand break repair occurs. We suggest that local density of damage induced and proximity of independent repair areas within the interphase nucleus determine the complexity of aberration resolved in metaphase. Overall, the most likely outcome of a single nuclear traversal of a single α-particle in CD34+ cells is a single chromosome aberration per damaged cell. As the incident LET of the α-particle increases, the likelihood of this aberration being classed as complex is greater.