Gene-Expression Biomarkers for Application to High-Throughput Radiation Biodosimetry

作者：M.B. Grace, Charles A. Salter, Jeffrey Bullard, P. G. S. Prasanna, G.L. Manglapus, William F. Blakely · 年份：2005 · 被引用次数：3 · 研究领域：Effects of Radiation Exposure、Radiation Therapy and Dosimetry、Carcinogens and Genotoxicity Assessment

Molecular biodosimetry tools are a valuable asset for life-saving medical triage and patient management fol-lowing a radiological or nuclear disaster. Even with the delayed onset of symptoms, sometimes several days after exposure, gene-expression biomarkers can identify these exposed individuals very early after exposure, allowing for prompt medical intervention. This early assessment of a radiation dose after exposure would en-hance the operational commander’s situational awareness of the radiation exposure status of deployed units and increase the prospect of reduced morbidity and mortality through early medical intervention. Candidate gene targets were selected from microarray studies of ex vivo-irradiated human peripheral blood lymphocytes and measured using a quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) assay in a human whole blood model at 24 and 48 hr post-irradiation (0.2 to 5.0 Gy 60Co-gamma rays at 0.1 Gy/minute). A multi-target QRT-PCR technique was optimized, an inter-individual variation study of an ex vivo response was expanded to include a larger cohort of healthy donors, and a collaborative study was con-ducted involving the in vivo response of cancer patients undergoing total body irradiation treatment. These validation studies illustrated that gamma radiation causes quantifiable and reproducible gene-expression changes in the radiation biomarker targets CDKN1A, BAX, GADD45A, and DDB2 over several days across a