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DNA Repair Genes Identified as Blood Radiation Indicators

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Medical and engineering researchers from Lawrence Berkeley National Lab in California and several universities identified eight genes that can provide a faster diagnosis of potential radiation exposure than current methods. The team led by Andrew Wyrobek of Berkeley Lab’s Life Sciences Division published its findings in a recent issue of the journal PLOS One.

The researchers say there is currently is no quick way to determine if people have been exposed to dangerous levels of radiation, from an event such as nuclear reactor accident or “dirty-bomb” explosion, nor can those methods quickly discriminate between radiation exposure versus an infection due to an injury or chemical exposure. Blood assays that track chromosomal changes or watching for the onset of physical symptoms can take several days, can be too late for people who could benefit from immediate treatment.

The Berkeley Lab team — with colleagues from Methodist Hospital Research Institute in Houston, Stanford University, Uniformed Services University of the Health Sciences, and University of California in Davis — focused on DNA, since DNA is a key target of radiation, and in particular the genes that carry out repair functions when DNA is damaged. When those DNA repair functions are restricted, detrimental health effects can be expected.

The researchers started with 40 genes that regulate expression of DNA-repair proteins, and examined the genes in blood samples taken from healthy people before and after exposing the samples to typical radiation doses received by radiotherapy patients. That initial screening led to 12 genes that had more than double the change in response after exposure. The researchers then isolated eight genes that had no overlap between unirradiated and irradiated samples.

Wyrobek and colleagues also treated the blood samples with lipopolysaccharide (LS), a bacterial toxin that mimics inflammatory stress. This LPS treatment allowed the researchers to account for gene-expression responses that could be interpreted as indicators of radiation exposure, but actually caused by injury or infection. In addition, the team irradiated a portion of these samples to learn how the genes respond to both inflammation and radiation.

The researchers validated their findings with two methods. First, they analyzed a separate data set of irradiated blood samples for the response of the eight genes to radiation exposure, and found a close match between their own data and the independent data set. The team then examined data from a large group of bone marrow transplant patients who received total-body radiation, and again found a close match between their data and the gene-expression responses of the patients after they received treatment.

Wyrobek envisions these results and other planned studies could lead a blood test with their biochemical markers administered by a hand-held device similar to glucose meters used by diabetes patients. This blood test could help emergency responders quickly identify people exposed to high radiation doses needing immediate treatment, as opposed to people exposed to lower radiation levels who only need monitoring.

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