Energy and dose-rate dependence of neoplastic transformation and mutations induced in mammalian cells by fast neutrons.

Since our original observation that low-dose, low-dose-rate JANUS neutrons produced more transformation in C3H 10T1/2 cells than equivalent doses at high dose rate (Hill, Buonaguro, Myers, Han, and Elkind, Nature 298, 67-69, 1982), there have been many reports on the dose-rate dependence of a variety of high-LET radiations. Some of these have qualitatively supported our original and subsequent observations, and some have found no evidence for a dose-rate effect. Thus there remain questions about the generality, size, tissue specificity, and reproducibility of these observations. Furthermore, there are no well-established mechanistic descriptions or observations to account for such effects. In this report studies are presented using a range of neutron energies produced by the UCLA cyclotron from 12- to 46-MeV protons on beryllium. In particular, emphasis is placed on comparing results between energies for neoplastic transformation and mutation end points, and preliminary data are presented on the molecular and mechanistic aspects of neutron-induced damage.