Preclinical experiments with the SIN negative pi-meson beam. RBE values for tumour and normal cell systems, and genetic damage studies in the beam peak and plateau regions

The results of radiobiological experiments made using the biomedical negative pion beam of the Swiss Institute for Nuclear Research (SIN) since it commenced operation at the end of 1974 are presented. In the radiobiological investigations, the intensity of the π- beam (180MeV/c) in the Bragg peak has been 3 to 5rad/min; contamination with electrons and muons is 13.5%. Only very sensitive systems have been chosen for study, for example healthy embryonic tissue damage in mice (irradiation in utero on 8th day of life) and inhibition of mitotic activity in mouse jejunum. As a sensitive tumour system, Ehrlich ascites carcinoma cells were irradiated in vitro at 40C, and they were inoculated into mice immediately after irradiation. The RBE values have depended on dose and were between 1.3 and 1.7. The ratios of the effects of the same doses in the peak and plateau regions of the beam showed clinically highly interesting values of 1.4 to 1.5. The nuclear damage (as events leading to cell death) were extensively studied in different mitotic stages of Drosophila germ cells. Nine different types of mutations, such as chromosome loss, loss of definite chromosome regions, lethals, translocations, etc., were determined. The RBE values varied between 0.4 and 3.3, depending on mutation type and cell stage. The existence of RBE values for peak pions under unity have suggested a new concept of high-LET-radiation action, namely to two-system theory. One system with high-LET, RBE=1 is characterized by a high O2-tension (euoxic cells) and high OER values (in addition to other phenomena); the other system with high-LET, RBE much >1 is characterized by hypoxia and natural radioresistance. (author)