NEUTRON-ENERGY-DEPENDENT MUTAGENESIS IN V79 CHINESE-HAMSTER CELLS

There has been a keen interest in the past decade in both elucidating the mutation frequency for different energy radiations and determining if mutation frequencies vary from one gene to another. This interest is driven in part by the strong link between mutational events and subsequent development of the carcinogenic state. Using fast neutrons produced by impinging protons on a beryllium target at the UCLA/VA cyclotron, we have examined the energy dependence of the induction of mutants at the hprt and tk loci. In this paper, we present studies using V79 Chinese hamster cells exposed to beams of neutrons produced from protons with 46, 30, 20 and 14 MeV energy. There is a gradually increasing cytotoxic effect of the neutrons as the energy decreases. In a similar fashion, the mutation frequency also shows a strong energy dependence with the frequency increasing as the energy decreases. The results also show that the frequency of induced mutants at the tk gene is higher than at the hprt gene. Calculations of RBE using gamma rays as the standard radiation showed a maximum for 14 MeV neutrons of 5.4 for the hprt locus and 36.6 for TK normal-growth mutants (TKng). Most of the curves for induction are best fitted with a linear function in the low-dose region with a few becoming curvilinear at higher doses.