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Transgenerational Effects of Chronic Low-Dose Irradiation in a Medaka Fish Model System

Colorado State University

Why this Project?

There are major gaps in our knowledge about genetically-based responses of living systems to low doses of ionizing radiation. These radiation-induced responses may be seen in parents or the offspring (transgenerational). The project will fill in these gaps at low doses and at low dose rates.

Project Goals

The overall goal of this project is to seek information on mechanisms involved in transgenerational changes in gene activity using Medaka fish and their progeny as a model. Mutation rates of microsatellite DNA, and the consequences of these changes induced by chronic irradiation will be examined. The project will accomplish this by:

  1. 1. Providing microarrays for the Medaka fish that will be used to identify genetic changes in progeny of radiated fish.
  2. Determining whether low doses or dose-rates of radiation administered to Medaka produce changes in expression of the genes in their unirradiated offspring or subsequent generations of progeny, and if so, whether these progeny show related changes in radiosensitivity.
  3. 3. Studying the changes in gene activity and correlated these changes with radiosensitivity when each generation of fish are maintained in a constant, chronic low-dose and low dose-rate radiation environment.

Experimental Approach

  1. Medaka specimens will be irradiated at selected dose-rates and total doses in the Low-Dose Radiation Facility at the Savannah River Ecology Laboratory (SREL). Studies on markers for mutations in microsatellite DNA from irradiated Medaka will be conducted at SREL. Colorado State University will measure changes in gene activity.
  2. Correlations between both large-scale exploratory microarray analysis and selected functional gene-by-gene analysis will be used to search for arrays of genes (and individual genes, such as repair gene homologs) in the Medaka fish that respond to low doses of radiation. Adult inbred strains of radiation resistant and sensitive Medaka fish, as well as in embryos at selected stages of development, will be studied.

Expected Outcomes

The results of these studies, as well as others using Medaka specimens, will be compared and discussed in workshops held at regular intervals to determine if trans-generational effects from low doses of radiation exist. If these effects can be detected, the mechanisms of their production and the impact of the trans-generational effects on cancer risk will be estimated. If changes are found, further studies will be conducted to determine whether these changes disappear when the chronic radiation environment is removed. This may provide information on the adaptive response and genetic instability noted in many other studies.

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