SPECTRUM OF MUTATION INDUCED BY IONIZING RADIATION 0

Project: Research project

Description

One of the prices we pay for living in an industrial and technological
society is exposure to a variety of chemical and radiation mutagens.
Examples of this exposure are contaminating levels of Cs-137 remaining from
the Chernobyl disaster and increased exposure to UV due to thinning of the
ozone layer. Both events are expected to result in increased numbers of
cancers. Although it is possible to readily detect this exposure if it
occurs at high dose, it is far more difficult to detect this exposure if it
occurs at low dose or if the possibility of exposure is raised after it has
occurred. One potential means of addressing this problem is to determine
the spectrum of mutations induced by a specific mutagen and then determine
if this spectrum is present in genomic DNA in cells taken from individuals
at risk. This grant proposal involves using a cultured mouse stem cell
system to determine more accurately the spectrum of mutation induced by
ionizing radiation. The first specific aim is to determine the mutational
spectrum induced by high dose high and low LET ionizing radiation and
compare and contrast this spectrum with those spectra produced by equally
genotoxic doses of UV and an alkylating chemical mutagen, as well as with
the spontaneous spectrum. Having defined the ionizing radiation spectrum,
the second specific aim is to determine the lowest possible dose at which
all or part of this spectrum can be recognized. The third and final
specific aim is to determine if the ionizing radiation induced mutational
spectrum is altered in morphologically differentiated cells derived from
the stem cells. Such a comparison has not been performed previously. The
mouse cell lines to be used are unique because they have heterozygous
deficiencies for the purine salvage gene aprt (adenine
phosphoribosyltransferase) and because they contain two chromosome 8
homologs, which harbor the aprt gene, that are distinguishable with a
molecular analysis. Cells with homozygous deficiencies, which will be
induced with the above mutagens, will be selected and a molecular analysis
used to elucidate and enumerate the spectrum of mutations. This molecular
analysis will include Southern blots, PCR, and DNA sequencing.
StatusFinished
Effective start/end date4/1/922/28/05

Funding

  • National Institutes of Health: $196,372.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $208,330.00
  • National Institutes of Health
  • National Institutes of Health: $202,262.00
  • National Institutes of Health
  • National Institutes of Health

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mutations
ionizing radiation
genes
mutagens
mutagenesis
dosage
mice
ataxia
cells
adenines
cultured cells
tumor suppressor genes
radiation
gamma rays
oncogenes
deoxyribonucleic acid
carcinogens
mammals
purines
sequencing

ASJC

  • Medicine(all)