Computer Simulation of FISH Data on Chromosome Aberrations
Produced by X-rays or Alpha Particles
Abstract
With fluorescent in situ hybridization (FISH)
many different categories of chromosome aberrations
can be recognized -- dicentrics, translocations, rings,
and various complex aberration types such as insertions or three-way
interchanges.
Relative frequencies for the various aberration categories
indicate radiation damage mechanisms and reflect radiation quality.
FISH data support a proximity version of the
classic random breakage-and-reunion model for aberration formation.
A Monte Carlo computer
implementation of the model, called CAS (chromosome aberration
simulator), is here generalized to high LET
and compared to published data on human cells irradiated with x-rays or
Pu238 alpha particles. For each kind of radiation,
CAS has two adjustable parameters: number of interaction
sites per cell nucleus and number of reactive DSBs per Gy.
Aberration frequencies for various painted chromosomes, of varying
lengths, and for eleven different categories of simple or complex
aberrations were simulated and compared to the data.
The optimal number of
interaction sites was found to be ~13 for x-irradiation and ~25 for
alpha-irradiation. The RBE for
reactive DSBs (which are a minority of all DSBs) was found to be ~4.
The two-parameter
CAS model adequately matches data on many different categories
of aberrations. It can use FISH data obtained with
any one painting pattern to predict
results for any other kind of FISH painting pattern or
whole-genome staining, and to estimate a suggested
over-all numerical damage indicator for chromosome aberration studies,
the total misrejoining number.
Radiation Research 148, S93-S101, 1997.
Allen M Chen**, Joe N. Lucas+, Paul J. Simpson#,
Carol S. Griffin#, John R. K. Savage#, David J. Brenner%,
Lynn R. Hlatky* and Rainer K. Sachs**.
**Dept. Mathematics, University of California, Berkeley, CA 94720.
+LLNL, Livermore, CA.
#MRC Radiation and Genome Stability Unit, Harwell, UK.
%Center for Radiological
Research, Columbia University, New York, NY.
*Joint Center for Radiation Therapy, Harvard Medical School,
Boston, MA.
Key words: Chromosome Aberrations; FISH;
LET; Computer Model; Monte Carlo Simulation; Biodosimetry.
alphas