Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles

Abstract

Purpose Cells of the lung are at risk from exposure to low and moderate doses of ionising radiation from a range of environmental and medical sources. To help assess human health risks from such exposures, a better understanding of the frequency and types of chromosome aberration initially-induced in human lung cell types is required to link initial DNA damage and rearrangements with transmission potential and, to assess how this varies with radiation quality. Materials and Methods We exposed normal human bronchial lung epithelial (NHBE) cells in vitro to 0.5 and 1 Gy low-linear energy transfer (LET) γ-rays and a low fluence of high-LET α-particles and assayed for chromosome aberrations in premature chromosome condensation (PCC) spreads by 24-colour multiplex-fluorescence in situ hybridisation (M-FISH). Results Both simple and complex aberrations were induced in a LET and dose dependent manner however, the frequency and complexity observed were reduced in comparison to that previously reported in spherical cell types after exposure to comparable doses or fluence of radiation. Approximately 1-2% of all exposed cells were categorised as being capable of transmitting radiation-induced chromosomal damage to future NHBE cell generations, irrespective of dose. Conclusion One possible mechanistic explanation for this reduced complexity is the differing geometric organisation of chromosome territories within ellipsoid nuclei compared to spherical nuclei. This study highlights the need to better understand the role of nuclear organisation in the formation of exchange aberrations and, the influence three-dimensional (3D) tissue architecture may have on this in vivo.