Workshop Draft Report: Molecular and Cellular Biology of Moderate Dose (1- 10 Sv) Radiation and Potential Mechanisms of Radiation Protection Bethesda, MD December 17-18, 2001 … … report prepared for the Workshop participants by the Radiation Research Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health. Contact individuals include: C. Norman Coleman , Philip Tofilon, Helen Stone, Rosemary Wong. Phone: 301-496-6111 or 301-496-6360; email addresses: ccoleman@mail.nih.gov; …

MOLECULAR AND CELLULAR BIOLOGY AND DETECTION OF RADIATION DAMAGE Summary of critical information Classical radiobiology is based on the paradigm that cell death results from DNA damage that occurs both directly in the form of strand breaks and indirectly as a result of oxidative reactions. In cells that survive, there is the potential for DNA mutations and chromosomal aberrations. Mutations and to some extent chromosomal alterations can be characterized at the molecular level, although their mechanisms of formation following radiation exposure remain to be fully defined. New techniques, especially those based on fluorescence in situ hybridization (FISH) allow for a more complete assessment of the genomic changes following radiation exposure. In addition, FISH should allow for the identification of informative biomarkers following exposure. However, it is now clear that radiation induces a variety of additional effects that can be expressed at cellular and tissue levels. These effects include the generation of oxidative stress, alterations in gene transcription, changes in signal transduction, and a number of epigenetic phenomena. The latter, to be described in more detail below, involve alterations in cells and tissue not directly related to a change in the structure of the DNA per se. Although a wide variety of events occur, their specific role in tissue radioresponse requires further investigation using a variety of model systems ranging from single cell mechanisms to complex multicellular models to in vivo organ and whole animal studies In addition to contributing to the fundamental understanding of radiation effects within tissue, evaluation of specific changes in gene expression or protein profiles in irradiated cells will likely provide a practical means of defining tissue exposure. Such information may identify sentinel genes or proteins that can serve as in vivo ‘bio-dosimeters’. This type of research is in its infancy. However, its advancement would likely provide a powerful tool for the accurate assessment of the individual risk within an exposed population and possibly determine appropriate pre- and post-exposure interventions. To clearly understand non-carcinogenic and carcinogenic radiation effects, it is necessary to understand multiple response pathways, including cell-cell and cell-microenvironment…

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