Physical, biophysical, and cell-biological factors that can contribute to enhanced neoplastic transformation by fission-spectrum neutrons

Abstract

In radiobiology, fission-spectrum neutrons frequently have been used as a surrogate for other high-LET radiations, particularly when thick absorbers were involved as in animal studies. However, the spectrum of proton secondaries, plus the gamma rays generated in the absorption processes, suggests that a characterization of such a beam, based upon an average LET alone, may not adequately account for the spectrum of biological properties that it may have. Conflicting results have been reported on the relative effectiveness of reduced dose rates of fission-spectrum neutrons, and other high-LET radiations, for the induction of noeplastic transformation of cells in culture. Enhanced rates of neoplastic transformation were reported for C3H 10T1/2 mouse cells, Syrian hamster embryo cells, and human hybrid cells-all with the same beam of fission-spectrum neutrons generated by the JANUS reactor at the Argonne National Laboratory. No enhancement was observed with C3H 10T1/2 cells exposed to the beam from the TRIGA reactor at the Armed Forces Radiobiological Research Institute, or to maximally effective alpha particles. The recent report that an enhancement was also observed when human hybrid cells were exposed at a low dose rate to the TRIGA beam indicated that physical factors alone were not responsible for the differences observed with C3H 10T1/2 cells exposed to these various beams. To resolve the lack of consistency in the results that had been reported, a biophysical model was developed based, in part, on the existence of a narrow age interval in the growth cycle of a cell during which it is particularly sensitive to radiation neoplastic transformation. Because of the special physical and biological properties of cells in M phase, and/or in late G2 phase or early G1 phase, these cohorts of cells were proposed as those that are hypersensitive to neoplastic transformation by radiation.