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(PP056) A novel biodosimetry method for measuring radiation-induced genetic damage.
Bacher, Jeff*,1, Halberg, Richard1, Megid, Wael1, Kent, Marijo1, Prolla, Tom2, 1 Genetic Analysis, Madison, WI, USA2 Genetics-Biotechnology Center, Madison, WI, USA
ABSTRACT- For extended space missions, exposure to galactic cosmic radiation and solar particle events poses a serious threat to the health of the astronauts. Dosimeters measure radiation exposure received but not its biological effects or individual differences in radiation sensitivity. Accurate methods for measuring the extent of genetic damage resulting from accumulated radiation exposure received by astronauts will be critical for estimating potential health risks and the need for countermeasures. The goal is to investigate the efficacy of a novel biodosimetry method for monitoring mutational load by testing for radiation-induced mutations in repetitive DNA sequences. Repetitive sequences constitute nearly one third of the human genome and some are extremely sensitive to radiation-induced mutations. Most repetitive sequences are in non-coding regions of the genome and, therefore, alterations in these loci are usually not deleterious to the survival of the host cell. Thus, mutations in noncoding repetitive sequences can accumulate, providing a stable molecular record of DNA damage from all past exposures. Progenitor stem cells are long lived and continually divide producing progeny cells. Mutations in repetitive DNA loci in progenitor stem cells will accumulate and through analysis of progeny blood or sperm cells can serve as biological sensors to monitor radiation-induced genetic damage. To test this we are: (a) screening a broad range of repetitive DNA sequences to identify genetic loci most sensitive to high-LET radiation-induced mutations, (b) testing whether radiation-induced mutations in progenitor stem cells are cumulative and that mutational load can be quantitatively measured by sampling a population of single or small pools of progeny blood, cheek or sperm cells for changes in repetitive DNA sequences, and (c) investigating possible mechanisms causing radiation-induced mutations in repetitive DNA loci. Our results indicate that mutational load profiling, may be useful for monitoring an individuals exposure to radiation and potential health risks.
Key words: biodosimetry, mutations, microsatellite, repeats
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