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Multidimensional
Analysis of Human Epithelial Cell Response to Low Dose Radiation
Mary Helen Barcellos-Hoff
Lawrence Berkeley National Laboratory
Berkeley, CA 94720
(Jointly funded by NASA and DOE)
Why
this Project?
To determine
the importance of the cells microenvironment on its radiation
response.
Project Goals:
To study
the changes in gene expression response to low-dose radiation
in a three-dimensional human mammary epithelial cell model.
This physiologically relevant system will make it possible to
study the signal transduction associated with cell-cell and
cell-matrix interactions as they impact gene expression and
radiation-induced changes in phenotype.
Experimental
Approach:
A consortium
of LBL investigators will employ high-throughput analysis of
gene expression patterns to identify the unique molecular pathways
of radiation responses. The proposed research will determine
both quantitative and qualitative differences in patterns of
gene expression as a function of dose and cellular environment.
The gene families and likely signaling pathways operational
in rapid responses will be identified. Persistent changes in
gene expression and alterations will be compared in cells hit
and in those not hit directly by radiation to determine how
the cellular matrix and cell communication alter potential bystanders
effects. The research will be extended to identify and characterize
soluble proteins that mediate secondary responses to radiation.
Expected
Outcomes:
This project
will provide cross comparisons of radiation responses using
the same cell model, thereby facilitating definition of the
role of increased interactions between cells and their microenvironment
in radiation sensitivity and risk.
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