Theory of pairwise lesion interaction

A comparison between repair time constants measured both at the molecular and cellular levels has shown that the DNA double strand break is the molecular change of key importance in the causation of cellular effects such as chromosome aberrations and cell inactivation. Cell fusion experiments provided the evidence that it needs the pairwise interaction between two double strand breaks - or more exactly between the two ''repair sites'' arising from them in the course of enzymatic repair - to provide the faulty chromatin crosslink which leads to cytogenetic and cytolethal effects. These modern experiments have confirmed the classical assumption of pairwise lesion interaction (PLI) on which the models of Lea and Neary were based. It seems worthwhile to continue and complete the mathematical treatment of their proposed mechanism in order to show in quantitative terms that the well-known fractionation, protraction and linear energy transfer (LET) irradiation effects are consequences of or can at least be partly attributed to PLI. Arithmetic treatment of PLI - a second order reaction - has also the advantage of providing a prerequisite for further investigations into the stages of development of misrepair products such as chromatin crosslinks. It has been possible to formulate a completely arithmetic theory of PLI by consequently applying three biophysically permitted approximations - pure first order lesion repair kinetics, dose-independent repair time constants and low yield of the ionization/lesion conversion. The mathematical approach will be summarized here, including several formulae not elaborated at the time of previous publications. We will also study an application which sheds light on the chain of events involved in PLI. (author)