Office of Biological and Environmental Research

DOE Low Dose Radiation Program Workshop IV

Abstract

Title: Genetic Variation in Tissue Responses to Low-Dose Radiation

Authors: E. M. Rinchik,^1,2 P. Hoyt,³ L. Branstetter,¹ R. Olszewski,¹ K. T. Cain,¹ and B. Voy^1,3

Institutions: ¹Life Sciences Division, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee; ²Department of Biochemistry, Cellular, and Molecular Biology, The University of Tennessee, Knoxville, Tennessee; ³The University of Tennessee–Oak Ridge National Laboratory Graduate School of Genome Science and Technology, Oak Ridge, Tennessee

The molecular responses of cells exposed to biological stimuli or insults (such as radiation, or chemical or biotoxins) vary with the type of exposure, dose, and dose rate, and the type, genetic constitution, and tissue/organ site of the exposed cell(s). We are combining basic principles of mouse genetics and substantial mouse genetic and mutation resources with new genomic technologies to address how individual genetic constitution affects tissue responses to low-dose radiation (LDR; 10 cGy) in the intact organism. Exposure of cells to LDR can induce or repress the expression of specific gene products. Our overall hypothesis that LDR responses will differ, to different extents, among individuals because of genetic variation in the genes/proteins that cooperate in effecting these responses. We are standardizing conditions for validating specific gene responses to LDR in different tissues of different genotypes, as well as testing global molecular response(s), initially using microarray technology, in various tissues from a number of genetically diverse inbred mouse strains and from known mutants. Selected reproducible variant LDR responses will be additionally studied by genetic segregation and mapping analyses to evaluate the degree of complexity (ranging from single-gene effects to quantitative traits) of the variant molecular response. Such molecularly characterized variant strains can be exploited in the future to test directly the relevance of any specific molecular response on overall cellular and/or whole-organism LDR phenotypes that may be altered by genetic or environmental factors.

[Research sponsored by the Low-Dose Radiation Research Program, Office of Biological and Environmental Research, U.S. Department of Energy, under contract DE-AC05-00OR22725 with UT-Battelle, LLC.]

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