title: Biodosimetry for High-Dose Exposures Based on Dicentric Analysis in Lymphocytes Released from the G2-Block by Caffeine.
abstract: High-dose assessments using the conventional dicentric assay are essentially restricted to doses up to 5 Gy and only to lymphocytes that succeed to proceed to first post-exposure mitosis. Since G2-checkpoint activation facilitates DNA damage recognition and arrest of damaged cells, caffeine is used to release G2-blocked lymphocytes overcoming the mitotic index and dicentric yield saturation problems, enabling thus dicentric analysis even at high-dose exposures. Using the fluorescence in situ hybridization technique with telomere and centromere peptide nucleic acid probes, the released lymphocytes, identified as metaphases with decondensed chromosomes following 1.5 h caffeine treatment, show increased yield of dicentrics compared to that obtained in lymphocytes that reach metaphase without G2-checkpoint abrogation by caffeine. Here, a 3-h caffeine/colcemid co-treatment before harvesting at 55 h post-exposure is used so that the dicentric analysis using Giemsa staining is based predominantly on lymphocytes released from the G2-block, increasing thus dicentric yield and enabling construction of a dose-response calibration curve with improved precision of high-dose estimates.
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Karachristou
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Karakosta
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pantelias
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Hatzi
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pantelias
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Thanassoulas
authors.affiliation: Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Karaiskos
authors.affiliation: Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Dimitriou
authors.affiliation: Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece gterzoudi@rrp.demokritos.gr.
authors.forename: Georgia I
authors.initials: GI
authors.lastname: Terzoudi
mesh_terms: D001681:Biological Assay / Q000379:methods; D002110:Caffeine / Q000008:administration & dosage*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D020732:Cytogenetic Analysis / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects*; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002110:Caffeine