Evolution of DNA damage in irradiated cells (Q1193312)

The paper presents a general class of continuous time Markov chain models, combining analytic and numerical methods, to describe the behaviour of DNA damage in irradiated cells. After the formalism of general Markov chains and of mathematical models, and after some examples presented in Sections 1 and 2, Section 3 is devoted to the post- irradiation period. For the post-irradiation behaviour, using the discrete time Markov chain embedded at transitions gives the ultimate distribution of damage more simply than does integrating the Kolmogorov forward equations. In a representative special case, explicit expressions for the probability distribution of damage at large times are given in the form used for numerical computations and comparisons with experiments on human lymphocytes. A principle of branching ratios, that late assays can only measure appropriate ratios of repair and interaction functions, not the functions themselves, is derived and discussed. Section 4 contains some discussions, and Section 5 other post-irradiation models. The results given in the present paper indicate that continuous time Markov chains provide a powerful and flexible approach to studying the time evolution of DNA damage caused by ionizing radiation. The results proved in this study have been applied in detail to experimental observations with some, though limited, success.