Why this Project?
To
address how individual genetic background affects tissue responses
to low dose radiation in the intact organism. It is known
that the molecular responses of cells exposed to biological
stimuli or insults (such as radiation or chemicals) vary with
the type of exposure, dose and dose rate of the insult and
the type, genetic constitution, and tissue-organ site of the
exposed cells.
Project Goals:
To
see if low dose radiation responses will differ among individuals
because of genetic variation in the genes/proteins that cooperate
in producing these responses.
Experimental Approach:
This
study will standardize conditions to validate specific gene
responses to low dose radiation in different tissues from
animals with different genotypes. Global molecular responses
will be tested in these animals. Microarray technology will
be used to measure radiation-induced changes in gene response
in various tissues from genetically diverse inbred mouse strains
and from mice with known mutations. Additionally, a mapping
analysis of genetic segregation will be done to molecularly
characterized variant strains of mice and determine reproducible
variant low dose radiation responses.
Expected Outcomes:
Variant
strains of mice with a range of genetic backgrounds will be
molecularly characterizes so that they can be used to directly
test the relevance of any specific radiation-induced molecular
response on phenotypes. Studies will be conducted to determine
how these responses can be altered by genetic or environmental
factors.
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