title: Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles.
abstract: OBJECTIVE
  Cells of the lung are at risk from exposure to low and moderate doses of ionizing 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.
  
  
  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-color multiplex-fluorescence in situ hybridization (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 categorized as being capable of transmitting radiation-induced chromosomal damage to future NHBE cell generations, irrespective of dose.
  
  
  CONCLUSIONS
  One possible mechanistic explanation for this reduced complexity is the differing geometric organization of chromosome territories within ellipsoid nuclei compared to spherical nuclei. This study highlights the need to better understand the role of nuclear organization in the formation of exchange aberrations and, the influence three-dimensional (3D) tissue architecture may have on this in vivo.
authors.affiliation: Centre for Cell Chromosome Biology.
authors.forename: Matthew
authors.initials: M
authors.lastname: Themis
authors.forename: Elisa
authors.initials: E
authors.lastname: Garimberti
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hill
authors.forename: Rhona M
authors.initials: RM
authors.lastname: Anderson
mesh_terms: D000512:Alpha Particles / Q000009:adverse effects*; D001980:Bronchi / Q000166:cytology*; D002869:Chromosome Aberrations / Q000528:radiation effects*; D002877:Chromosomes, Human / Q000528:radiation effects; D004249:DNA Damage; D004847:Epithelial Cells / Q000378:metabolism* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects*; D015321:Gene Rearrangement / Q000528:radiation effects; D006801:Humans; D018499:Linear Energy Transfer