### 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 language | English (US) |
---|---|

Pages (from-to) | 1579-1588 |

Number of pages | 10 |

Journal | International Journal of Radiation Biology |

Volume | 76 |

Issue number | 12 |

State | Published - 2000 |

Externally published | Yes |

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### 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

*International Journal of Radiation Biology*,

*76*(12), 1579-1588.

**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.

Research output: Contribution to journal › Article

*International Journal of Radiation Biology*, vol. 76, no. 12, pp. 1579-1588.

}

TY - JOUR

T1 - Random breakage and reunion chromosome aberration formation model; an interaction - Distance version based on chromatin geometry

AU - Sachs, R. K.

AU - Levy, D.

AU - Chen, A. M.

AU - Simpson, P. J.

AU - Cornforth, Michael

AU - Ingerman, E. A.

AU - Hahnfeldt, P.

AU - Hlatky, L. R.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033635874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033635874&partnerID=8YFLogxK

M3 - Article

C2 - 11133039

AN - SCOPUS:0033635874

VL - 76

SP - 1579

EP - 1588

JO - International Journal of Radiation Biology

JF - International Journal of Radiation Biology

SN - 0955-3002

IS - 12

ER -