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International Journal of Radiation Biology, 74, 185-206, 1998

Double-Strand Break Misrejoining After X-Irradiation:
Relating Moderate to Very High Doses by a Markov Model


Key words: Markov model, DSB misrejoining, PFGE, chromosome aberrations, low LET.
Abstract

Double-strand break (DSB) misrejoinings, observed with pulsed-field gel electrophoresis (PFGE) after x-irradiation of human cells at very high doses (80--160 Gy), are related to chromosome aberration dose-response relations at moderate doses (1--5 Gy) by the Sax-Markov binary eurejoining/misrejoining (SMBE) model. The SMBE model applies Sax's breakage-and-reunion scenario to a subset of DSBs active in binary misrejoining and in binary eurejoining (accidental restitution). The model is numerically consistent with both chromosome aberration data and the PFGE data if proximity effects (restrictions on the range of DSB free end interactions) are present. Proximity effects are modeled by partitioning the cell's nucleus into approximately 400 interaction sites, with two active DSB free ends capable of rejoining only if they were produced within the same site. Neglecting one-track action, the SMBE model predicts a quadratic-linear (QL) low LET dose-response relation for DSB misrejoining, i.e. there is a quadratic response at moderate doses, which becomes linear as the dose becomes large, rather than vice-versa. The linear region results because at very high doses almost all of the active DSB free ends misrejoin rather than eurejoin.

Radiation Research, 149, 59-67, 1998. Tomas Radivoyevitch*, David G. Hoel*, Allen M. Chen+ and Rainer K. Sachs+. *Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC 29425; +Department of Mathematics, University of California, Berkeley, CA 94720. Corresponding author: Tomas Radivoyevitch, Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC 29425 USA; tel: 803-766-7064; fax: 803-792-0539; e-mail: radivot@musc.edu.
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