title: Mechanistic models.
abstract: Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (i) "interaction" of lesions produced by statistically independent particle tracks, (ii) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (iii) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the repair-misrepair (RMR) and lethal-potentially-lethal (LPL) models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate, as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations, are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.
authors.affiliation: Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, University of California, Berkeley.
authors.forename: S B
authors.initials: SB
authors.lastname: Curtis
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D008433:Mathematics; D008954:Models, Biological; D011830:Radiation Effects
chemical_list: D004247:DNA