Random breakage and reunion chromosome aberration formation model; an interaction - Distance version based on chromatin geometry

R. K. Sachs, D. Levy, A. M. Chen, P. J. Simpson, M. N. Cornforth, E. A. Ingerman, P. Hahnfeldt, L. R. Hlatky

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Purpose: Using published FISH data for chromosome aberration production in human fibroblasts by hard X-rays to test a breakage-and-reunion model. Methods: The model assumed pairwise misrejoining, random apart from proximity effects, of DNA double-strand break (DSB) free ends. CAS (chromosome aberration simulator) Monte Carlo computer software implementing the model was modified to use a distance algorithm for misrejoining instead of using DSB interaction sites. The modification (called CAS2) allowed a somewhat more realistic approach to large-scale chromatin geometry, chromosome territories and proximity effects. It required adding a third adjustable parameter, the chromosome territory intersection factor, quantifying the amount of intertwining among different chromosomes. Results: CAS2 gave somewhat better results than CAS. A reasonable fit with a few discrepancies was obtained for the frequencies at three different radiation doses of many different aberration types and of aberrations involving various specific chromosomes in a large data set using one-paint FISH scoring. The optimal average chromosome territory intersection factor was ~ 1.1, indicating that, for an arbitrarily chosen location in the nucleus, on average slightly more than two chromosomes have very nearby loci. Without changing the three parameter values, a fit was also obtained for a corresponding, smaller, two-paint data set. Conclusions: A random breakage-and-reunion model incorporating proximity effects by using a distance algorithm gave acceptable approximations for many details of hard X-ray aberration patterns. However, enough discrepancies were found that the possibility of an additional or alternate formation mechanism remains.

Original languageEnglish (US)
Pages (from-to)1579-1588
Number of pages10
JournalInternational Journal of Radiation Biology
Volume76
Issue number12
DOIs
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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