Developing a scientific basis for radiation risk estimates: goal of the DOE Low Dose Research Program.

The U.S. Department of Energy's Low Dose Radiation Research Program is a 10 y activity currently funded at $21 million per year. It focuses on biological responses to low doses (<0.1 Gy) of low-LET ionizing radiation. The overall goal of this program is to provide a sound scientific basis for the radiation protection standards. The program supports basic research that combines modern genomic, molecular, and cellular techniques with recent advances in scientific instrumentation. These combinations make it possible to detect responses and test paradigms associated with the mechanisms of low dose radiation action not previously measurable or testable. Research to date is briefly reviewed and suggests the need for some major paradigm shifts. Exposure of the extracellular matrix can modify both the pattern of gene expression and the phenotype of the cells which result in cell transformation without direct mutation. Low dose radiation exposure results in a range of dose-response relationships for changes in the number, types, and patterns of gene expression. Such studies suggest an increased role for gene expression relative to single mutations for radiation induced cancer. Low dose research using microbeams demonstrated that cells do not require a direct "hit" to result in significant biological alterations. These "bystander effects" demonstrate that "non-hit" cells respond with changes in gene expression, DNA repair, chromosome aberrations, mutations, and cell killing. Research to link genomic instability with cancer is also being conducted and will be discussed. Detection of radiosensitivity genes as markers of genetic susceptibility in individuals and populations can be used in epidemiological studies to determine how molecular changes may impact risk. It is not possible to determine how this research will influence current radiation standards. However, the Low Dose Research Program will help ensure that radiation standards are set using the best scientific data available, and that they are adequate and appropriate for the protection of workers and the public.