title: Computational model of dose response for low-LET-induced complex chromosomal aberrations.
abstract: Experiments with full-colour mFISH chromosome painting have revealed high yield of radiation-induced complex chromosomal aberrations (CAs). The ratio of complex to simple aberrations is dependent on cell type and linear energy transfer. Theoretical analysis has demonstrated that the mechanism of CA formation as a result of interaction between lesions at a surface of chromosome territories does not explain high complexes-to-simples ratio in human lymphocytes. The possible origin of high yields of γ-induced complex CAs was investigated in the present work by computer simulation. CAs were studied on the basis of chromosome structure and dynamics modelling and the hypothesis of CA formation on nuclear centres. The spatial organisation of all chromosomes in a human interphase nucleus was predicted by simulation of mitosis-to-interphase chromosome structure transition. Two scenarios of CA formation were analysed, 'static' (existing in a nucleus prior to irradiation) centres and 'dynamic' (formed in response to irradiation) centres. The modelling results reveal that under certain conditions, both scenarios explain quantitatively the dose-response relationships for both simple and complex γ-induced interchromosomal exchanges observed by mFISH chromosome painting in the first post-irradiation mitosis in human lymphocytes.
authors.affiliation: Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin Str. 4, 119334 Moscow, Russia National Research Nuclear University MEPhI, Kashirskoye Shosse 31, 115409 Moscow, Russia.
authors.forename: Y A
authors.initials: YA
authors.lastname: Eidelman
authors.affiliation: Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin Str. 4, 119334 Moscow, Russia National Research Nuclear University MEPhI, Kashirskoye Shosse 31, 115409 Moscow, Russia andreev_sg@mail.ru.
authors.forename: S G
authors.initials: SG
authors.lastname: Andreev
mesh_terms: D002467:Cell Nucleus / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000528:radiation effects*; D020223:Chromosome Painting; D002877:Chromosomes, Human / Q000528:radiation effects*; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000528:radiation effects; D018499:Linear Energy Transfer / Q000528:radiation effects*; D008214:Lymphocytes / Q000528:radiation effects*; D008938:Mitosis / Q000528:radiation effects; D008962:Models, Theoretical