HIGH-LET RADIATION CARCINOGENESIS - WHAT DO WE KNOW AND WHAT DO WE NEED TO KNOW

In the more than four decades since experimental evidence suggested th at neutrons have a greater carcinogenic effect than low LET radiations , a large number of studies have been carried out with high LET radiat ions. While we still do not know the mechanisms, it is perhaps timely to examine what we do know about high LET radiation carcinogenesis and what remains to be determined. In this paper, the basic physical aspe cts of high LET radiation interactions in tissue are characterised and some general features of dose-response curves for the induction of ca ncer are discussed. Physical and biological factors that could determi ne the shapes and other general features of the curves are delineated. In place of the much used traditional concepts, such as dose, LET, an d RBE, it is suggested that a deeper understanding be sought within th e framework of the physical events that occur, their frequency distrib utions, and their possible biological consequences on a cellular and s ubcellular scale. As an example of such an approach, the tumour preval ence data for the mouse Harderian gland exposed to a number of radiati ons, ranging from Co-60 gamma rays to very heavy ions, are considered. A detailed analysis of physical events is presented for irradiation b y 600 MeV.amu-1 Fe ions. The study enables one to make an assessment o f factors that determine the shape of dose-response relations, such as target size and number, particle fluence rate, cell killing, and indi vidual animal susceptibility. Finally, some answers to the questions i n the title are suggested.