| Recent high dose pulsed field gel electrophoresis (PFGE) data (Lobrich et al. (1995) Proc. Natl. Acad. Sci. 92, pp 12050-12054) of X-irradiated human fibroblasts is used to select the the Sax histone (SH) model as an adequate mathematical representation of misrejoining DNA double-strand breaks (DSBs). The SH model supports the notion that DSB misrepair results from the random recombination of completely disconnected (active) DSB free ends. A low dose extension of the SH model, the Sax-Markov binary eurepair (SMBE) model, predicts a linear-quadratic-linear misrepair dose response that is consistent with chromosomal aberration data.; Two existing induced DNA fragment distribution models, the ethidium bromide (EtBr) model and the specific probe model, are derived in detail using direct and indirect methods. These models describe a cell's DNA fragment distribution immediately after an acute exposure to low LET irradiation, but not after a significant amount of misrepair has occurred. To describe DNA fragments in misrepaired cells, this research develops the Sax histone EtBr (SHEB) model, an extension of the EtBr model to include the DSB misrepair dynamics of the SH model. The SHEB model is thoroughly analyzed for exponentially distributed (high dose) initial conditions. |
