DOE Low Dose Radiation Research Program Workshop I Abstracts November 10-12, 1999, Washington, D.C.

Charles R. Geard, A.S. Ballajee, T.K. Hei, B. Ponnaiya, and S. Marino
Center for Radiological Research, Columbia University, New York, NY, USA
crg4@columbia.edu

Summary: A recently developed means of delivering charged particles to precise sites in or near cells [a microbeam], will be used to define the relative contributions of specific sub-cellular and/or extra-cellular sites to the damaging effects of known numbers of particles, including 1, the lowest possible radiation dose.

Abstract: The genetic, carcinogenic and cytotoxic effects of ionizing radiations have been assumed for many years to have their source in the direct induction of damage to DNA in the nuclei of cells. This basic paradigm has come into question in recent years as a consequence of studies with very low doses of alpha particles and of other studies with irradiated media. These findings of effects on presumably non-hit and hence not directly damaged cells has been termed a bystander effect. In no instance however could it be determined with any degree of certainty which cells were actually hit with a particle or where. We have developed a charged particle microbeam which provides a level of precision in terms of numbers of particles, sites of placement of particles, and temporal delivery of particles which is unattainable with conventional radiation sources. That is, we have the means to address questions about the bystander effect in a definitive manner. Human fibroblasts have been irradiated with known numbers of particles through cell membranes, cytoplasm, nuclei and medium [trans-nuclear]; membranes, cytoplasm and medium [trans- cytoplasmic] and adjacent to cells [trans- medium]. In this way the relative contributions of each component in the cellular milieu to irradiation will be defined. Experiments to date have provided definitive proof of the reality of a radiation bystander effect but relative contri-butions of the components of the response pathway remain to be determined. Hence a basic paradigm in defining radiation responsiveness which is the basis for low dose extrapolations in the establishment of protection standards is under challenge.