Alpha-Particle-Induced Sister Chromatid Exchange in Normal Human Lung Fibroblasts: Evidence for an Extranuclear Target

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Abstract
We investigated the relationship between nuclear hits by alpha particles and the subsequent occurrence of sister chromatid exchanges (SCEs) in normal human diploid lung fibroblasts (HFL1). Cells were exposed to 238Pu alpha particles at doses ranging from 0.4-12.9 cGy and subsequently analyzed for SCEs. A significant increase in SCE frequency was observed even at the lowest dose examined. The extent of induction of SCEs in the HFL1 cells showed dose dependency in the very low dose range, i.e. 0.4-2.0 cGy. Thereafter, induction of SCEs was independent of dose. Based on measurements of the nuclear areas of the HFL1 cells in conjunction with target theory calculations, the lowest dose resulted in an approximately 8.6-fold increase in the percentage of cells showing excessive SCEs over the theoretically expected percentage of cells whose nuclei were calculated to be traversed by one or more alpha particles. The extent of the discrepancies between theoretically expected and experimentally observed frequencies of SCEs became progressively reduced with increasing radiation dose. We additionally determined that SCEs induced by the alpha particles have no significant dependency on the time of cell collection after exposure to a selected dose of alpha particles, thereby confirming that the differences between the theoretically predicted and observed SCE frequencies were not due to an artifact of the time of cell sampling for the SCE measurements. These results obtained with normal human cells are similar to those of other investigators who observed excessive SCEs in immortalized rodent cells beyond that which could be attributed exclusively to nuclear traversals by alpha particles. Such consistent findings point to the existence of an alternative, extranuclear target through which alpha particles cause DNA damage, as detected by SCE analysis. The existence of an extranuclear compartment as a target for alpha particles may have important implications for the susceptibility of lung cells to the DNA-damaging effects of alpha-particle exposure due to the inhalation of radon progeny.

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