Mechanisms for the biological effectiveness of high-LET radiations.

Radiations of high linear energy transfer (LET) have long been known to have greater biological effectiveness per unit dose than those of low LET, for a wide variety of biological effects. However, values of relative biological effectiveness depend considerably on the biological system and in some instances the values are clearly below unity. The differences between high- and low-LET radiations may be due to many factors, almost all of which are related to radiation track structure in one way or another, and some can in principle lead to qualitative as well as quantitative differences between the radiations. Explanations for LET-dependent differences in effectiveness are discussed over a variety of levels from the multicellular and cellular scale down to the DNA scale, with illustrations from radiobiological data. Information from well-defined slow light ions provide particularly useful analytic data, but practical issues extend also to neutrons and fast heavy ions, which may compound high- and low-LET features. It is suggested that effectiveness of the radiation is determined predominantly by the complex clustered damage that it produces in DNA, but that for high-LET radiations long-term effects are in some instances limited by single-track-survival probabilities of the traversed cells.