ENERGY DEPOSITION MECHANISMS AND BIOCHEMICAL ASPECTS OF DNA STRAND BREAKS BY IONIZING-RADIATION

A theoretical model based on physical, chemical, and biochemical mechanisms has been presented to evaluate the yields of DNA strand breaks (single and double) as a function of linear energy transfer (LET) or - dE/dx. Energetic heavy charged particles are considered explicitly to provide a general theory for low- as well as for high-LET rediation. There are three main features of the calculation: (a) track structure considerations for the energy deposition pattern, (b) three-dimensional structure of DNA molecules to provide information on the exact location of damage, and (c) a Monte-Carlo scheme to simulate the diffusion processes of water radicals. To avoid the complexities of a cellular medium, an aqueous solution of DNA is considered in the calculation. When the results of the calculations are compared with experimental measurements of the yields of strand breaks in mammalian DNA (exposed in a cellular complex), reasonable agreement is obtained. However, only those experimental data have been compared where there were no enzyme repair processes. The method of calculation has also been extended to study breaks in higher-order structures of DNA molecules such as chromatin. Specific limitations of the present model have been pointed out for making further improvements.