Biomarkers of DNA Damage: A Topic and Patent Review
Beatrix A. Olofsson and Jane Azizkhan-Clifford
Affiliation: Drexel University College of Medicine, MS 497, Room 11101 New College Building, 245 N. 15th Street,Philadelphia, PA 19102, USA.
The integrity of the human genome is threatened by DNA damaging agents, particularly ionizing radiation, which induces potentially lethal double strand breaks. Ionizing radiation is of particular concern given its increasing use in medical diagnostic imaging and given the risk of radiological attack or exposure from nuclear reactor accidents. As biological responses to DNA damage have been elucidated, numerous biomarkers have emerged to potentially serve as biodosimeters of radiation exposure and effects. A brief background on the need for biodosimeters of DNA damage and of the DNA damage response is included. DNA damage biomarkers have many possible applications, including monitoring patients and health care workers exposed in diagnostic imaging, monitoring effectiveness and recovery in patients receiving chemotherapy and/or radiation therapy to inform dosing and scheduling, and establishing individual exposure in populations exposed to a radiological hazard. Recent patents on biomarkers of DNA damage discussed in this review include: antibody based tests of proteins modified in response to DNA damage; RNA and protein marker profiles identified from analysis of genome-wide expression and metabolite screens; and genetic markers of damage sensitivity. Applications, advantages and limitations of each biomarker are discussed.
Keywords: ATM, biodosimeters, DNA damage, double strand break, gene expression, ionizing radiation, phosphorylation, DNA DAMAGE SIGNALING PATHWAY, H2AX, DNA Damage Biomarkers
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