Radiation
exposure can influence changes in gene expression. This
project will examine radiation-induced up and down regulation
of gene expression as a function of radiation dose, type,
dose-rate, tissue type and exposure conditions. This will
provides basic data to determine how radiation alters
gene expression and will lead to understanding the genes
and pathways involved in the induction and repair of radiation-induced
damage. This evaluation is essential in development of
models to extrapolate risk from high doses where disease
is observed to lower doses where it is difficult to determine
risk or damage.
Project
Goals:
Determine
the number and types of genes that change in their expression
following low and high doses of radiation.
Determine
if the biological mechanisms associated with radiation
induced damage are similar after exposure to high and
low doses.
Characterize
the changes in gene expression as a function of tissue
type, exposure conditions and radiation type.
Experimental Approach:
Changes
in stress-responsive genes weremeasured after low doses
of radiation using modern molecular fluorescent cDNA microarray
hybridization techniques that rapidly and accurately measure
many samples taken at the same time. The genes, CDKN1A
and GADD45 increased their expression of protein, as a
linear function of the dose delivered. The increase in
gene expression measured with the gene chips was compared
to the increase using standard gene expression techniques
and was shown to be closely related. These data provided
the necessary positive controls to extend the studies
to other experimental conditions. The expression of multiple
genes is being monitored using this chip technology. Changes
are being measured in multiple tissues of animals exposed
to radiation in vivo. The changes in gene expression are
being characterized as a function of time after exposure,
dose-rate and radiation type. These studies are being
expanded to using human tissues and cells to help extrapolate
the responses from animals to humans.
Expected Outcomes:
Evaluation
of the role of dose on gene expression.
Determination
if the mechanism of response of cells to high and low
radiation dose is the same.
Conversion
of the changes observed in gene expression into functional
changes of biological significance.
Development
of a biological marker of radiation exposure and dose
using the microarray technique.
