title: Complex chromosome aberrations in peripheral blood lymphocytes as a potential biomarker of exposure to high-LET alpha-particles.
abstract: OBJECTIVE
  To determine the induction and transmission, to second and third division cells, of complex chromosome aberrations in peripheral blood lymphocytes after exposure to high-LET alpha-particles in vitro.
  
  
  METHODS
  Separated peripheral blood lymphocytes collected from four healthy donors were irradiated in vitro with either high-LET alpha-particles (121 keV/microm; 0.5 Gy) or low-LET X-rays (250kV constant potential; 3 Gy). Cells were harvested in first, second and third division post-irradiation and chromosome aberrations observed at each cell division were analysed by combining the techniques of FISH and DAPI/Hoechst 33258 harlequin staining. Whole chromosome probes were used for chromosomes 1, 2 and 5, together with a pan-centromeric probe and the resulting chromosome 'painting' patterns were classified according to the Savage and Simpson (S & S) scheme (Savage and Simpson 1994a, Savage and Tucker 1996).
  
  
  RESULTS
  A greater proportion of complex chromosome aberrations was observed, defined as involving three or more breaks in two or more chromosomes, relative to total exchanges, after exposure to 0.5 Gy alpha-particles (mean 1 track/cell) than after the high reference dose of 3 Gy X-rays (49-56% and 20-22%, respectively). Qualitatively, alpha-particles induced chromosome aberrations of far greater complexity than those observed after X-rays. This was reflected by both the rapid reduction in the percentage of damaged cells between first and second division indicative of cell death, and the spectrum of aberration types observed in second and third division cells post-irradiation. Regardless of this complexity, 15% of the complexes induced by alpha-particles at first division were potentially transmissible and by third division, transmissible-type complexes, specifically insertions, represented the predominant complex type (65%).
  
  
  CONCLUSIONS
  Transmissible-type complexes were observed, specifically insertions, in both second and third division cells after exposure to high-LET alpha-particles (0.5 Gy) in vitro. The authors predict these cells to be stable and to be capable of persisting through many cell generations. Considering that the induction of complex chromosome aberrations by low-LET radiation is strongly dependent on dose, so that they are expected to be undetectable at environmental exposures, insertions are much more likely to be a characteristic feature of high-LET radiation at all doses. From this the usefulness of insertions as biomarkers of past exposure to environmentally relevant doses of high-LET alpha-particles is supported.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, Chilton, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Anderson
authors.forename: S J
authors.initials: SJ
authors.lastname: Marsden
authors.forename: E G
authors.initials: EG
authors.lastname: Wright
authors.forename: M A
authors.initials: MA
authors.lastname: Kadhim
authors.forename: D T
authors.initials: DT
authors.lastname: Goodhead
authors.forename: C S
authors.initials: CS
authors.lastname: Griffin
mesh_terms: D000512:Alpha Particles; D015415:Biomarkers; D002453:Cell Cycle / Q000528:radiation effects; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007211:Indoles; D018499:Linear Energy Transfer; D008214:Lymphocytes / Q000528:radiation effects*
chemical_list: D015415:Biomarkers; D007211:Indoles; C007293:DAPI