title: Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.
abstract: In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB) can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI). However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79-100%) compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16-43%), suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation.
authors.affiliation: Division of Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina, United States of America.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Meadows
authors.forename: Holly K
authors.initials: HK
authors.lastname: Dressman
authors.forename: Pamela
authors.initials: P
authors.lastname: Daher
authors.forename: Heather
authors.initials: H
authors.lastname: Himburg
authors.forename: J Lauren
authors.initials: JL
authors.lastname: Russell
authors.forename: Phuong
authors.initials: P
authors.lastname: Doan
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: Joseph
authors.initials: J
authors.lastname: Lucas
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011833:Radiation Injuries, Experimental; D011839:Radiation, Ionizing; D014916:Whole-Body Irradiation / Q000009:adverse effects