title: Chromosome aberration measurements in mitotic and G2-PCC lymphocytes at the standard sampling time of 48 h underestimate the effectiveness of high-LET particles.
abstract: The relationship between heavy-ion-induced cell cycle delay and the time-course of aberrations in first-cycle metaphases or prematurely condensed G(2)-cells (G(2)-PCC) was investigated. Lymphocytes of the same donor were irradiated with X-rays or various charged particles (carbon, iron, xenon, and chromium) covering an LET range of 2-3,160 keV/μm. Chromosome aberrations were measured in samples collected at 48, 60, 72, and 84 h postirradiation. Linear-quadratic functions were fitted to the data, and the fit parameters α and β were determined. At any sampling time, α values derived from G(2)-cells were higher than those from metaphases. The α value derived from metaphase analysis at 48 h increased with LET, reached a maximum around 155 keV/μm, and decreased with a further rise in LET. At the later time-points, higher α values were estimated for particles with LET > 30 keV/μm. Estimates of α values from G(2)-cells showed a similar LET dependence, yet the time-dependent increase was less pronounced. Altogether, our data demonstrate that heavily damaged lymphocytes suffer a prolonged G(2)-arrest that is clearly LET dependent. For this very reason, the standard analysis of aberrations in metaphase cells 48 h postirradiation will considerably underestimate the effectiveness of high-LET radiation. Scoring of aberrations in G(2)-PCC at 48 h as suggested by several authors will result in higher aberration yields. However, when particles with a very high-LET value (LET > 150 keV/μm) are applied, still a fraction of multiple damaged cells escape detection by G(2)-analysis 48 h postirradiation.
authors.affiliation: Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Planckstrasse 1, 64291, Darmstadt, Germany.
authors.forename: Ryonfa
authors.initials: R
authors.lastname: Lee
authors.forename: Elena
authors.initials: E
authors.lastname: Nasonova
authors.forename: Carola
authors.initials: C
authors.lastname: Hartel
authors.forename: Marco
authors.initials: M
authors.lastname: Durante
authors.forename: Sylvia
authors.initials: S
authors.lastname: Ritter
mesh_terms: D002869:Chromosome Aberrations / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016195:G2 Phase / Q000528:radiation effects*; D020450:Heavy Ions / Q000009:adverse effects; D006801:Humans; D018499:Linear Energy Transfer; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D008677:Metaphase / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects*; D013997:Time Factors