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

ABSTRACT

Domestic, low-level exposure to radon gas is considered a major environmental lung-cancer hazard involving DNA damage to bronchial cells by alpha particles from radon progeny. At domestic exposure levels, the relevant bronchial 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 bronchial 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 unfeasible, resulting in uncertainty in extrapolations of risk from high to domestic radon levels. A technique to assess the effects of single alpha particles uses a charged-particle microbeam, which irradiates individual cells or cell nuclei with predefined exact numbers of particles. Although previously too slow to assess the relevant small oncogenic risks, recent improvements in throughput now permit microbeam irradiation of large cell numbers, allowing the first oncogenic risk measurements for the traversal of exactly one alpha particle through a cell nucleus. Given positive controls to ensure that the dosimetry and biological controls were comparable, the measured 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 (involving cellular traversal by multiple alpha particles) may overestimate low-level (involving only single alpha particles) radon risks.