Mutagenic effects of a single and an exact number of α particles in mammalian cells

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single α particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1⁻ mutants induced in human–hamster hybrid (A_L) cells by either a single or an exact number of α particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1, 2, 4, or 8 α particles at a linear energy transfer of 90 keV/μm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A_L cells (survival fraction ≈ 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10⁵ survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single α particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.