Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death

The frequency of chromosome aberrations per traversal of a nucleus by a cha rged particle at the low dose limit increases proportionally to the square of the linear energy transfer (LET), peaks at about 100 keV/mu m and then d ecreases with further increase of LET. This has long been interpreted as an excessive energy deposition over the necessary energy required to produce a biologically effective event. Here, we present an alternative interpretat ion. Cell traversed by a charged particle has certain probability to receiv e lethal damage leading to direct death. Such events may increase with an i ncrease of LET and the number of charged particles traversing the cell. Ass uming that the lethal damage is distributed according to a Poisson distribu tion, the probability that a cell has no such damage is expressed by e(-cLx ), where c is a constant, L is LET, and x is the number of charged particle s traversing the cell. From these assumptions, the frequency of chromosome aberration in surviving cells can be described by Y = alpha SD + beta (SD2) -D-2 With the empirical relation Y = alpha D + beta D-2 in the low LET regi on, where S = e(-cL), alpha is a value proportional to LET, beta is a const ant, and D is the absorbed dose. This model readily explains the empiricall y established relationship between LET and relative biological effectivenes s (RBE). The model can also be applied to clonogenic survival. If cells can survive and they have neither unstable chromosome aberrations nor other le thal damage, the LET-RBE relationship for clonogenic survival forms a humpe d curve. The relationship between LET and inactivation cross-section become s proportional to the square of LET in the low LET region when the frequenc y of a directly lethal events is sufficiently smaller than unity, and the i nactivation cross-section saturates to the cell nucleus cross-sectional are a with an increase in LET in the high LET region.