The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei

Domestic, low-level exposure to radon gas is considered a major environment al lung-cancer hazard involving DNA damage to bronchial cells by alpha part icles from radon progeny. At domestic exposure levels, the relevant bronchi al cells are very rarely traversed by more than one alpha particle, whereas at higher radon levels-at which epidemiological studies in uranium miners allow lung-cancer risks to be quantified with reasonable precision-these br onchial cells are frequently exposed to multiple alpha-particle traversals. Measuring the oncogenic transforming effects of exactly one alpha particle without the confounding effects of multiple traversals has hitherto been u nfeasible, resulting in uncertainty in extrapolations of risk from high to domestic radon levels. A technique to assess the effects of single alpha pa rticles uses a charged-particle microbeam, which irradiates individual cell s or cell nuclei with predefined exact numbers of particles, Although previ ously too slow to assess the relevant small oncogenic risks, recent improve ments in throughput now permit microbeam irradiation of large cell numbers, allowing the first oncogenic risk measurements for the traversal of exactl y one alpha particle through a cell nucleus. Given positive controls to ens ure that the dosimetry and biological controls were comparable, the measure d oncogenicity from exactly one alpha particle was significantly lower than for a Poisson-distributed mean of one alpha particle, implying that cells traversed by multiple alpha particles contribute most of the risk. If this result applies generally, extrapolation from high-level radon risks (involv ing cellular traversal by multiple alpha particles) may overestimate low-le vel (involving only single alpha particles) radon risks.