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Developing point of care and high-throughput biological assays for determining absorbed radiation dose.
MedLine Citation:
PMID:  21724286     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Systems are being developed to assess radiation exposure based on leukocyte mRNA levels obtained by finger-stick sampling. The goal is to provide accurate detection of dose exposures up to 10Gy for up to 1week following exposure. We previously showed that specific mRNA sequences increase expression within an hour of exposure, and some genes continue to show elevated expression for at least 24h. Full duration and dose-dependence of this persistence remain to be determined. In the present study, real-time quantitative PCR (qPCR) was used to determine changes in gene expression. qPCR can rapidly analyze small blood samples and could be adopted into a field-portable instrument that provides a radiation dose readout within 30min. MATERIALS AND METHODS: From previous microarray analysis of 21,000 genes expressed in human lymphoblastoid cells 4h post-irradiation (0-4Gy), 118 genes were selected for evaluation by qPCR of gene expression in the leukocytes of human blood irradiated in vitro with doses of 0-10Gy from a Co-60 gamma source at a dose rate of 30cGy/min. RESULTS: Blood from 20 normal healthy human donors yielded many mRNA sequences that could be used for radiation dosimetry. We observed four genes with large and persistent responses following exposure: ASTN2, CDKN1A, GADD45A, and GDF15. Five genes were identified as reliably non-responsive and were suitable for use as endogenous controls: DPM1, ITFG1, MAP4, PGK1, and SLC25A36; of these, ITFG1 was used for the analyses presented here. A significant dose-responsive increase in expression occurred for CDKN1A that was >16-fold at 10Gy and 3-fold at 0.5Gy compared to pre-irradiation values. CONCLUSIONS: These data show large, selective increases in mRNA transcript levels that persist for at least 48h after single exposures between 0.5 and 10Gy. Stable, non-responsive mRNA sequences for use as endogenous controls were also identified. These results indicate that following further study to establish the most reproducible gene and dose-response models under a wide range of conditions in vivo, rapid real-time qPCR on blood samples could potentially be used to establish biologically-effective dosimetry from either accidental irradiation or clinical radiotherapy.
Authors:
Michael C Joiner; Robert A Thomas; William E Grever; Joseph M Smolinski; George W Divine; Andre A Konski; Gregory W Auner; James D Tucker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-1
Journal Detail:
Title:  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology     Volume:  -     ISSN:  1879-0887     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8407192     Medline TA:  Radiother Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Dept. of Radiation Oncology, Wayne State University, Detroit, USA.
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