A theory is presented that provides an explanation for the observed features of the survival of cultured cells after exposure to densely ionizing high-linear energy transfer (LET) radiation. It starts from a phenomenological postulate based on the linear-quadratic form of cell survival observed for low-LET radiation and uses principles of statistics and fluctuation theory to demonstrate that the effect of varying LET on cell survival can be attributed to random variation of dose to small volumes contained within the nucleus. A simple relation is presented for surviving fraction of cells after exposure to radiation of varying LET that depends on the α and β parameters for the same cells in the limit of low-LET radiation. This relation implies that the value of β is independent of LET. Agreement of the theory with selected observations of cell survival from the literature is demonstrated. A relation is presented that gives relative biological effectiveness (RBE) as a function of the α and β parameters for low-LET radiation. Measurements from microdosimetry are used to estimate the size of the subnuclear volume to which the fluctuation pertains.

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