The ultimate goal of this investigation is to understand the mechanisms underlying the biological effects of combined treatments of low-linear-energy-transfer (LET) and high-LET radiations. In order to accomplish this goal, we will first study the effects of low-LET and high-LET radiation separately to establish their differences. Radiation-induced mammalian DNA single- and double-strand breaks, two of the few major DNA lesions, and their repair kinetics will be measured and characterized in detail. The rates of rejoining of these breaks inflicted by gamma-rays, fast neutrons, and their combinations will be contrasted. The effects on the rejoining kinetics will be compared with cellular repair measurements, including repair of potentially lethal damage (PLD). Between these end points, damage and repair at the chromosomal level will be examined. Furthermore, single cells will be employed for exploring the modes of cell killing in their progeny. From these parallel studies, the existence of eurepair and misrepair may be inferred or identified. Thus, the biological relevance of these processes may be implicated. Alkaline elution, hydroxylapatite uncoiling chromatography and neutral elution are the techniques that will be utilized for the DNA strand break assays. Premature chromosome condensation with viral fusogen will be employed for the aberration experiments. A semi-automated light-microscopy system is proposed for the single cell studies.
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