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Genetic Background Significantly Alters the Response to Low Dose Ionizing Radiation In Vivo

Brynn H. Voy
Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN.

Why this Project?

Genetic background influences an individual’s response to biological stimuli and is thought to impact the consequences of exposure to ionizing radiation. Because inbred strains of laboratory mice differ from each other genetically in a way that parallels the differences between human populations, they are suitable models in which to probe the effects of genetic background on radiation risk and to map locations of genes that modify the radiation response.

Project Goal

To identify genes that influence the reaction of different organs and individuals to ionizing radiation.

Experimental Approach

  1. Six common inbred strains of mice - C57Bl6 (B6), DBA/2, A/J, Balb/c, B6.C and C3H/HeJ - were exposed to low (10 cGy) or to high (200 cGy) doses of gamma radiation.
  2. Dorsal skin, spleen, thymus and testis were harvested either 1 or 3.5 hours after exposure.
  3. Microarrays representing 21,547 unique mouse genes are used to identify gene expression patterns altered by radiation.
  4. Genes altered by radiation independent of strain and by interaction between strain and radiation are identified from statistical data analysis using mixed model 2-factor ANOVA.

Outcomes

  1. The results from this study indicate that spleen and skin exhibit divergent responses to ionizing radiation in terms of the functional classes of genes that are differentially expressed.
  2. The numbers and identities of differentially expressed genes vary considerably between strains of mice, reveling that genetic background exerts a significant impact upon radiation-induced gene expression profiles.
  3. The data is continuing to be analyzed to better characterize the potential biological differences that define each strain’s response to radiation in skin and spleen. In summary these data highlight the degree to which genetic background impacts the initial response to ionizing radiation, as defined by altered patterns of gene expression, and underscore the need for further studies on the radiation response of mouse models with varied genetic composition.
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