Ionizing radiations have been shown to be able to induce the death of mammalian cells and initiate mutagenic or carcinogenic change. While all three end points are related through chromosomal changes, the latter in particular is of profound concern to human populations. We have undertaken a series of studies wherein mammalian cells were irradiated with low fluences of charged particles (protons, deuterons, helium ions) of defined LET from 10 to about 200 keV per micrometer. Frequencies of induced chromosomal changes were related to fluence at each LET, such that the induction of chromosomal changes per cell per charged particle could be estimated. However, for human exposures from densely ionizing radiation, such as the alpha particles from radon daughters, effects are dominated by the traversal of cells by single particles. Conventional experiments inevitably result in cells being exposed to a distribution (Poisson) of particle traversals. As the effect is unlikely to be a linear function of the number of traversals, a preferred approach would be to irradiate cells with exactly one (or any known number) of particles. To this end we are developing a dedicated beam line (microbeam) on a 4.2 MV Van de Graaff accelerator such that individual particles will vertically traverse individual living mammalian cells positioned by a microscope-based imaging system under computer control. "Conventional" low-fluence and "single-particle" studies will be compared, allowing critical evaluations of the potential of individual high LET charged particles to initiate change. This will have particular relevance both to consideration of the human health risks of radon daughter alpha particles and of basic mechanisms of chromosome aberration formation.
