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, Michael Cornforth, E. A. Ingerman, P. Hahnfeldt, L. R. Hlatky

Research output: Contribution to journalArticle

30 Citations (Scopus)

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
StatePublished - 2000
Externally publishedYes

Fingerprint

Reunion
chromosome aberrations
chromatin
chromosomes
Chromosomes
Aberrations
Chromosome Aberrations
Chromatin
Geometry
geometry
aberration
Paint
paints
interactions
strands
intersections
simulators
X-radiation
X-Rays
Double-Stranded DNA Breaks

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

Random breakage and reunion chromosome aberration formation model; an interaction - Distance version based on chromatin geometry. / Sachs, R. K.; Levy, D.; Chen, A. M.; Simpson, P. J.; Cornforth, Michael; Ingerman, E. A.; Hahnfeldt, P.; Hlatky, L. R.

In: International Journal of Radiation Biology, Vol. 76, No. 12, 2000, p. 1579-1588.

Research output: Contribution to journalArticle

Sachs, RK, Levy, D, Chen, AM, Simpson, PJ, Cornforth, M, Ingerman, EA, Hahnfeldt, P & Hlatky, LR 2000, 'Random breakage and reunion chromosome aberration formation model; an interaction - Distance version based on chromatin geometry', International Journal of Radiation Biology, vol. 76, no. 12, pp. 1579-1588.
Sachs, R. K. ; Levy, D. ; Chen, A. M. ; Simpson, P. J. ; Cornforth, Michael ; Ingerman, E. A. ; Hahnfeldt, P. ; Hlatky, L. R. / Random breakage and reunion chromosome aberration formation model; an interaction - Distance version based on chromatin geometry. In: International Journal of Radiation Biology. 2000 ; Vol. 76, No. 12. pp. 1579-1588.
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