PNNL

Abstract

Implicit in understanding the biological effects of ionizing radiation and subsequent risks associated with such exposure is that only cells “hit” by the radiation are likely to carry the legacy of radiation damage. When a cell is “hit” the deposition of energy can result in direct damage to the genetic material or indirect damage to critical nuclear targets through the radiolysis of water (Figure 1). The subsequent action of DNA repair processes either removes the lesion(s), or fixes the induced damage such that all surviving progeny of an irradiated cell carry the burden of radiation exposure, e.g., a gene mutation and/or a chromosomal rearrangement (Figure 1A). This central tenet in our understanding of the biological effects of ionizing radiation has now been called into question by the description of a number of non-targeted effects associated with radiation exposure. These effects can occur in the progeny of irradiated cells generations after the initial exposure, and/or in cells that were not directly traversed by ionizing radiation, but were some distance from the “hit” cells (reviewed in 1, 2) (Figure 1B). The work of Belyakov and colleagues in this issue of PNAS demonstrates for the first time non-targeted bystander responses in a three-dimensional human tissue model system (3). The investigators use a microbeam to deliver defined numbers of charged particles, in this case alpha particles - the type of radiation associated with radon decay, with high accuracy to precise locations (4, 5). A defined area of cells was irradiated in a thin vertical plane, ~two cell diameters, to bisect the tissue sample. Because of the inherent nature of the alpha particles there is very little radiation scatter. Consequently cells more than a few microns away from the plane of irradiated cells receive zero radiation dose. At 72 hours post irradiation, the tissues were formalin fixed, paraffin embedded, and sectioned in strips at increasing distances parallel to the plane of irradiated cells. This allowed analysis of tissue slices containing only non-irradiated cells at known distances from the plane of irradiated cells. Unirradiated cells up to 1 mm away from the irradiated cells, ~50-75 cell diameters distant, showed a significant enhancement in the measured fractions of apoptotic and micronucleated cells.