Chromosomal alterations in basic mechanisms of radiation injury

Colorado State University, Fort Collins CO

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Abstract

DESCRIPTION (provided by applicant): Chromosomal aberrations figure prominently as the underlying cause of many untoward biological effects caused by exposure to ionizing radiation (IR). These include acute effects responsible for cell and organism death, as well as delayed effects, principally cancers, that arise years post-irradiation. Current technology (e.g., whole chromosome painting) permits adequate detection of most large-scale chromosomal events that occur between different chromosomes, such as translocations. However, in order to advance our understanding of basic mechanisms of radiation injury, there is a need to improve the sensitivity and resolution of detection of smaller scale events, such as the complementary processes of mis-rejoining of DNA double strand breaks (DSBs) that can occur within an arm of a given chromosome, and which lead to either small deletions or inversions. By facilitating an increased understanding of the contribution of these "cryptic" chromosomal changes, the studies proposed here will provide valuable clues into the processes involved in IR-induced injury to the genome and its biological consequences. Such an understanding will ultimately serve to guide the design and timing of possible intervention strategies following accidental exposure or terrorist attack. By facilitating increased detection and understanding of the contribution of "cryptic" intra-chromosomal changes (interstitial deletions and inversions), the studies proposed here will provide valuable clues into the processes involved in ionizing radiation-induced injury to the genome and its biological consequences. Such an understanding will ultimately serve to guide the design and timing of possible intervention strategies following accidental exposure or terrorist attack.