Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases.
OBJECTIVE
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 gamma-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.


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.
Vazquez
M
M
Department of Mathematics, MC3840, University of California, Berkeley 94720, USA. mariel@math.berkeley.edu
Greulich-Bode
K M
KM
Arsuaga
J
J
Cornforth
M N
MN
Brückner
M
M
Sachs
R K
RK
Hlatky
L
L
Molls
M
M
Hahnfeldt
P
P
D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects* / Q000648:ultrastructure*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008214:Lymphocytes / Q000648:ultrastructure; D008677:Metaphase; D008957:Models, Genetic; D009010:Monte Carlo Method; D012984:Software; D013997:Time Factors