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PARENT SESSION

Genomic Maintenance & Repair

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP324) A complex dietary supplement dramatically reduces radiation-induced chromosome aberrations and H2AX foci in mice expressing elevated free radical processes.

Lemon, Jennifer*,1, Rollo, C. David2, Boreham, Douglas1, 1 Medical Physics and Applied Radiaions Sciences, Hamilton, ON, Canada2 Biology, Hamilton, ON, Canada

ABSTRACT- The repair of double-strand breaks (DSB) is critical for the maintenance of genomic integrity. Chromosome aberrations are often the byproduct of unrepaired or misrepaired DSBs, and have been linked to higher risk of carcinogenesis, abnormal cell function and increased sensitivity to endogenous metabolic free radical production and DNA damaging agents. Mice expressing elevated endogenous free radical processes (TGM) are significantly more radiosensitive than normal mice as indicated by significantly increased number of chromosome aberrations when exposed a 2Gy in vivo whole body dose of gamma radiation. A complex dietary supplement designed to offset oxidative stress and associated cellular processes (i.e. inflammation, mitochondrial function and membrane integrity) dramatically reduces radiation-induced chromosome aberrations in both TGM and normal mice. We postulate that the process associated with the reduction in radiation-induced chromosome aberrations corresponds to an increased scavenging of free radicals generated by ionizing radiation. To determine if this mechanism plays a significant role in reducing DNA damage, and hence the number of DSBs, we are examining the number of H2AX foci generated in supplemented and unsupplemented TGM and normal mice. H2AX migrates to DSBs as part of the repair complex and rapidly disassembles when repair is complete. Although it′s exact function is still under dispute, these properties makes H2AX an ideal marker for determining both the amount of DNA damage (number of foci) and the rate of DNA repair (rate of foci disappearance). We will present data regarding the effects of our complex dietary supplement on chromosome aberration and its modulation of H2AX foci formation

Key words: complex dietary supplement, chromosome aberrations, H2AX foci, ionizing radiation


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2005 RRS