Biomarkers for human radiation exposure

Abstract

There is a concern over the potential use of radioactive isotopes as a weapon of terror. The detonation of a radiation dispersal device, the so-called "dirty bomb" can lead to public panic. In order to estimate risks associated with radiation exposure, it is important to understand the biological effects of radiation exposure. Based on this knowledge, biomarkers to monitor potentially exposed populations after a radiological accident can be developed and would be extremely valuable for emergency response. While the traditional radiation exposure biomarkers based on cytogenetic assays serve as standard, the development of rapid and noninvasive tests for radiation exposure is needed. The genomics based knowledge is providing new avenues for investigation. The examination of gene expression after ionizing radiation exposure could serve as a potential molecular marker for biodosimetry. Microarray based studies are identifying new radiation responsive genes that could potentially be used as biomarkers of human exposure to radiation after an accident.

Dose-specific transcriptional responses in thyroid tissue in mice after 131I administration

“…3). Previously suggested 102 biomarkers for radiation were evaluated in the present dataset (Table 3) [7,8,21,22]. The majority of these genes (88/102) were not detected at any absorbed dose level in our data, and none of the gene was detected at all absorbed dose levels.…”

“…Transcriptional profiling with microarrays enables detection of global mRNA variation in tissues in a single experiment. The majority of studies using genome-wide approaches have been performed in vitro using gamma radiation and often at few absorbed dose levels or temporal points [7,8]. In contrast, studies performed in vivo have demonstrated complex and distinct dosedependent cellular responses following irradiation.…”

Comparative Analysis of Transcriptional Gene Regulation Indicates Similar Physiologic Response in Mouse Tissues at Low Absorbed Doses from Intravenously Administered211At

“…The differential expression of 56 radiation-associated genes proposed by Snyder and Morgan (15) and Chaudhry (16) showed low response levels at 24 h after 211 At injection. Only 19 genes showed significant regulation at least in 1 tissue (Fig.…”

“…The microarray assay facilitates a genome-wide study on transcriptional gene regulation in response to stimulus without the risk of excluding regulatory pathways by focusing on a designated set of genes for detecting a presupposed response (13,14). Furthermore, most studies focusing on radiation-induced transcriptional changes for the establishment of biomarkers have been performed in vitro (15,16). This gap in basic knowledge and the increasing interest in 211 At for radionuclide therapy demand further research in the field of normal-tissue damage, which offers a new venue for optimizing treatment protocols and improving acute and long-term risk assessment.…”

Ionizing radiation biomarkers for potential use in epidemiological studies

“…Most of these studies used blood cells (peripheral blood mononuclear cells, whole blood, cultured lymphocytes) for radiation doses between 0.5 and 10 Gy, over a time period between 4 and 24 h. Again, from these studies it is evident that genes involved in p53-regulated pathways are the best suited predictors of radiation exposure [160,[164][165][166][167][168][169]. Whether this would also be the case for other cell types or tissues, remains to be investigated.…”