TY - JOUR
T1 - Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases
AU - Vazquez, M.
AU - Greulich-Bode, K. M.
AU - Arsuaga, J.
AU - Cornforth, M. N.
AU - Brückner, M.
AU - Sachs, R. K.
AU - Hlatky, L.
AU - Molls, M.
AU - Hahnfeldt, P.
N1 - Funding Information:
The authors are grateful to J.T. Holman and K. Song for discussions. Research supported by NSF grant DMS 9969 (M7V an1d J1A), NSF grant DMS 96831(9PH6),NSF grant DBI 90924and8NH4I grant CA86823 (LH), NIH grant GM 5752and4 DOE grant DE-FG03-00-ER62909 (RKS), by the Bundesministerium für Veteirdigung, FGR (FV: INSAN I 096-38007)V(KG, MB and MM), and by NIH grant 7602(MC6).
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Purpose: To analyse spectra of chromosome aberrations induced in vitro by low LET radiation, in order to characterize radiation damage mechanisms quantitatively. Methods: Multiplex fluorescence in situ hybridization (mFISH) allows the simultaneous identification of each homologous chromosome pair by its own colour. mFISH data, specifying number distributions for colour junctions in metaphases of human peripheral blood lymphocytes 72 hours after exposure in vitro to a 3 Gy γ-ray dose, were combined with similar, previously published results. Monte Carlo computer implementations of radiobiological models for chromosome aberration production guided quantitative analyses, which took into account distribution of cells among different metaphases and lethal effects or preferential elimination of some aberrations at cell division. Results and Conclusions: Standard models of DNA damage induction/repair/misrepair explain the main trends of the data as regards the fraction of metaphases having a particular number of colours involved in colour junctions. However, all standard models systematically under-predict the observed fraction of metaphases where a large number of different chromosomes participate in aberrations. An early appearance of chromosomal instability could explain most of the discrepancies.
AB - Purpose: To analyse spectra of chromosome aberrations induced in vitro by low LET radiation, in order to characterize radiation damage mechanisms quantitatively. Methods: Multiplex fluorescence in situ hybridization (mFISH) allows the simultaneous identification of each homologous chromosome pair by its own colour. mFISH data, specifying number distributions for colour junctions in metaphases of human peripheral blood lymphocytes 72 hours after exposure in vitro to a 3 Gy γ-ray dose, were combined with similar, previously published results. Monte Carlo computer implementations of radiobiological models for chromosome aberration production guided quantitative analyses, which took into account distribution of cells among different metaphases and lethal effects or preferential elimination of some aberrations at cell division. Results and Conclusions: Standard models of DNA damage induction/repair/misrepair explain the main trends of the data as regards the fraction of metaphases having a particular number of colours involved in colour junctions. However, all standard models systematically under-predict the observed fraction of metaphases where a large number of different chromosomes participate in aberrations. An early appearance of chromosomal instability could explain most of the discrepancies.
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U2 - 10.1080/09553000210166354
DO - 10.1080/09553000210166354
M3 - Article
C2 - 12556338
AN - SCOPUS:0036904932
SN - 0955-3002
VL - 78
SP - 1103
EP - 1115
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 12
ER -