Experimental Radiation Carcinogenesis: What Have We Learned?

The data from a number of relatively large-scale animal experiments that were designed to examine the effects of dose rate, fractionation, and radiation quality are now accumulating. Apart from the answers obtained to the questions that the experiments were designed to elucidate there are a number of lessons to be learned about experimental design, the inadequacies of current models, and the areas of our ignorance and misconceptions. There is no single mechanism of radiation carcinogenesis. The induction of the initial events of tumorigenesis may be similar in most tumor types, whereas the factors influencing expression vary. In experimental animals radiation may (1) advance the time of appearance of a specific tumor type, (2) induce tumors by direct action on the target cells, or (3) induce tumors by a complex action on both the target and other tissues. The effect of dose rate will depend on the mechanism involved. It has become clear that dose-response curves for neutron irradiation "bend over" at low doses which makes the estimate of the initial slope difficult. The precise contribution of various factors influencing the shape of the curves is not clear. Because of the marked variation in the shape of dose-response curves for low-LET radiation, RBE values vary almost infinitely.