Gene expression signatures that predict radiation exposure in mice and humans.
BACKGROUND
The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.


RESULTS
We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans.


CONCLUSIONS
We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.
Dressman
Holly K
HK
Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina, United States of America.
Muramoto
Garrett G
GG
Chao
Nelson J
NJ
Meadows
Sarah
S
Marshall
Dawn
D
Ginsburg
Geoffrey S
GS
Nevins
Joseph R
JR
Chute
John P
JP
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure; D005260:Female; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000528:radiation effects; D005796:Genes / Q000528:radiation effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000528:radiation effects; D008403:Mass Screening; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010315:Particle Accelerators; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000235:genetics; D011839:Radiation, Ionizing; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D013045:Species Specificity; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D014916:Whole-Body Irradiation / Q000009:adverse effects
D003520:Cyclophosphamide; D004247:DNA; D014740:Vidarabine; C024352:fludarabine