Computer simulations of mFISH chromosome aberration data for human lymphocytes subjected to low-LET radiation: mechanistic imp

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International Journal of Radiation Biology , 2002. In press

Computer analysis of mFISH chromosome aberration data

uncovers an excess of very complicated metaphases

Mariel Vázquez*, Karin M. Greulich-Bode^a,b, Javier Arsuaga*, Michael N. Cornforth^d, Martina Brückner^a, Rainer K. Sachs*, Lynn Hlatky^c, Michael Molls^a and Philip Hahnfeldt^c

*Department of Mathematics, MC3840, University of California, Berkeley, CA 94720

^{aDepartment of Radiation Oncology, Technical University of Munich, Germany
^{bDepartment of Skin Carcinogenesis, German Cancer Research Center, Heidelberg, Germany
^{cDFCI, Harvard Medical School, Boston, MA 02115
^{dDepartment of Radiation Oncology, University of Texas Medical Branch, Galveston, TX 77555-0656

Correspondence to: Mariel Vázquez,
UC Berkeley, Mathematics Department, Berkeley, CA 94720-3840, USA.}}}}

Telephone: 510-642-2091; Fax: 510-642-8204; e-mail: mariel@math.berkeley.edu

► Abstract

Purpose. To analyze 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 color. mFISH data, specifying number distributions for color junctions in metaphases of human peripheral blood lymphocytes 72 hours after exposure in vitro to a 3 Gy g -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 colors involved in color 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.