title: Accumulation of DSBs in gamma-H2AX domains fuel chromosomal aberrations.
abstract: DNA double strand breaks (DSBs) pose a severe hazard to the genome as erroneous rejoining of DSBs can lead to mutation and cancer. Here, we have investigated the correlation between X irradiation-induced gamma-H2AX foci, theoretically induced DSBs, and the minimal number of mis-rejoined DNA breaks (MNB) in irradiated lymphocytes obtained from two healthy humans by painting of the whole chromosome complement by spectral karyotyping. There were less gamma-H2AX foci/dose than theoretically expected, while misrepair, as expressed by MNB/gamma-H2AX focus, was similar at 0.5 and 1Gy but 3.6-fold up at 3Gy. Hence, our results suggest that X-ray-induced gamma-H2AX foci in G0 lymphocyte nuclei contain more than one DSB and that the increasing number of DSBs per gamma-H2AX repair factory lead to an increased rate of misrepair.
authors.affiliation: Bundeswehr Institute of Radiobiology, Neuherbergstrasse, 11, D-80937 Munich, Germany. scherth@web.de
authors.forename: H
authors.initials: H
authors.lastname: Scherthan
authors.forename: L
authors.initials: L
authors.lastname: Hieber
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: V
authors.initials: V
authors.lastname: Meineke
authors.forename: H
authors.initials: H
authors.lastname: Zitzelsberger
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D019457:Chromosome Breakage; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006657:Histones / Q000032:analysis / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D007621:Karyotyping; D008214:Lymphocytes / Q000528:radiation effects / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D016192:Resting Phase, Cell Cycle; D014965:X-Rays
chemical_list: C468783:H2AX protein, human; D006657:Histones