title: Truly incomplete and complex exchanges in prematurely condensed chromosomes of human fibroblasts exposed in vitro to energetic heavy ions.
abstract: Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon silicon ions, or iron ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 degrees C for 24 h after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Incomplete and complex exchanges were analyzed in the irradiated samples. To verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole-chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after irradiation with the heavy ions of high LET, and consequently the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/microm, the highest LET included in the present study. For samples exposed to 200 MeV/nucleon iron ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique, which allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy iron ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges; these ratios were higher than those obtained after exposure to 6 Gy gamma rays. After 0.7 Gy of iron ions, most complex aberrations were found to involve three or four chromosomes, which is a likely indication of the maximum number of chromosome domains traversed by a single iron-ion track.
authors.affiliation: National Space Biomedical Research Institute, Baylor College of Medicine, NASA Johnson Space Center, Houston, Texas 77058, USA. hwu@ems.jsc.nasa.gov
authors.forename: Honglu
authors.initials: H
authors.lastname: Wu
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Kerry
authors.initials: K
authors.lastname: George
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawata
authors.forename: Francis A
authors.initials: FA
authors.lastname: Cucinotta
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000706:statistics & numerical data*; D002877:Chromosomes, Human / Q000187:drug effects / Q000528:radiation effects* / Q000648:ultrastructure*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects*; D005720:Gamma Rays; D005787:Gene Frequency / Q000187:drug effects / Q000528:radiation effects; D020450:Heavy Ions; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007501:Iron; D018499:Linear Energy Transfer; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D012825:Silicon
chemical_list: D008387:Marine Toxins; D010080:Oxazoles; C059041:calyculin A; D007501:Iron; D012825:Silicon