Abstract
<title>Abstract</title> <p>The reduction in biological effectiveness at high linear energy transfer (LET), commonly referred to as the overkill effect, remains an active area of investigation in high-LET radiobiology. Here, we present a statistical-mechanical framework in which attenuation emerges from the progressive occupancy of a finite population of radiation-sensitive chromatin domains. An effective free-energy formalism is used to describe the equilibrium occupancy state, yielding an LET-dependent occupancy fraction and an attenuation function representing the fraction of chromatin domains remaining available for the formation of additional biologically independent lethal events. The model predicts a continuous occupancy transition accompanied by a fluctuation maximum, identifying a characteristic LET range in which occupancy effects become most pronounced. When combined with a previously published LET-dependent damage-production model for carbon-ion irradiation of V79 cells, the framework predicts a maximum in lethal-lesion yield followed by a decline despite continued increases in damage production. A qualitative comparison with published relative biological effectiveness (RBE) data reproduces the characteristic rise, maximum, and subsequent decrease in biological effectiveness. These results suggest that finite chromatin-domain occupancy may provide a possible physical interpretation of attenuation, the overkill effect, and the emergence of an RBE maximum.</p>