A translatable predictor of human radiation exposure.

Abstract

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

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Citation

Published Version (Please cite this version)

10.1371/journal.pone.0107897

Publication Info

Lucas, Joseph, Holly K Dressman, Sunil Suchindran, Mai Nakamura, Nelson J Chao, Heather Himburg, Kerry Minor, Gary Phillips, et al. (2014). A translatable predictor of human radiation exposure. PLoS One, 9(9). p. e107897. 10.1371/journal.pone.0107897 Retrieved from https://hdl.handle.net/10161/10977.

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Scholars@Duke

Chao

Nelson Jen An Chao

Donald D. and Elizabeth G. Cooke Cancer Distinguished Research Professor

My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.

For more information see http://ed-media.mc.duke.edu/BMT.nsf


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