Long-term genomic instability in human lymphocytes induced by single-particle irradiation

Recent evidence suggests that genomic instability, which is an important st ep in carcinogenesis, may be important in the effectiveness of radiation as a carcinogen, particularly for high-LET radiations. Understanding the biol ogical effects underpinning the risks associated with low doses of densely ionizing radiations is complicated in experimental systems by the Poisson d istribution of particles that ran be delivered, In this study, we report an approach to determine the effect of the lowest possible cellular radiation dose of densely ionizing at particles, that of a single particle traversal . Using microbeam technology and an approach for immobilizing human T-lymph ocytes, we have measured the effects of single alpha -particle traversals o n the surviving progeny of cells. A significant increase in the proportion of aberrant cells is observed 12-13 population doublings after exposure, wi th a high level of chromatid-type aberrations, indicative of an instability phenotype, These data suggest that instability may be important in situati ons where even a single particle traverses human cells. (C) 2001 by Radiati on Research Society.