The aim of this proposal is to investigate theoretically some biological consequences of the initial yield and spatial distribution of radiation-induced free radicals. Free radicals are involved in various aspects of the cellular response to radiation, including cell killing, DNA strand breaks and chromosome aberration. The lifetime of these radical species is very short (nanoseconds), therefore the inhomogeneous initial spatial distribution of the radicals will still be manifest at the time of their interaction with biological material. It is proposed to start from calculated initial distributions of species caused by the radiation, then simulate, covering the next few nanoseconds, the non-homogeneous diffusion and interaction of these species with each other and with other biological and non-biological species. In particular, in view of the potential relevance of the exygen effect to high LET radiotherapy, the variation in the OER with LET will be investigated. In order to do this three stages are planned: Firstly, the physico-chemical techniques, available for simulating the initial formation, diffusion and interaction of the small numbers of species, will be refined and verified for application to high LET. Secondly, possible mechanisms for the initial production of oxygen by high LET particles will be theoretically examined and incorporated into the diffusion and interaction code, to compare with recent experiments on the variation of oxygen yield with LET. Thirdly, with the aid of the above-mentioned computer codes, using a stochastic, radical scavenging model for the oxygen effect, the question of whether the increasing yield of initial oxygen with LET does account for the variation of OER will be addressed. It is anticipated that the realistic treatment of the initial conditions and modes of radical interaction will allow a more reliable quantitative assessment of the various early mechanisms of radiation action. Particular results of interest in this work will be the variation in effectiveness of radiation-modifiers - such as oxygen, protectors and sensitizers - with radiation quality.
| Brenner, D J (1990) Track structure, lesion development, and cell survival. Radiat Res 124:S29-37 |
| Brenner, D J (1988) On the probability of interaction between elementary radiation-induced chromosomal injuries. Radiat Environ Biophys 27:189-99 |
| Brenner, D J (1987) Concerning the nature of the initial damage required for the production of radiation-induced exchange aberrations. Int J Radiat Biol Relat Stud Phys Chem Med 52:805-9 |
| Brenner, D J; Zaider, M; Geard, C R et al. (1987) Cell survival and plating efficiency. Radiat Res 111:572-6 |
| Brenner, D J; Bird, R P; Zaider, M et al. (1987) Inactivation of synchronized mammalian cells with low-energy X rays--results and significance. Radiat Res 110:413-27 |
