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Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.

Meadows SK, Dressman HK, Daher P, Himburg H, Russell JL, Doan P, Chao NJ, Lucas J, Nevins JR, Chute JP - PLoS ONE (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina, United States of America.

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.

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Prediction of radiation status of partially irradiated mice based upon the TBI gene expression profiles.(A) Diamonds represent control (non irradiated) samples, circles are exposure to AH, triangles are exposure to PH and Xs represent exposure to HL. Different dose levels were tested (blue = non-irradiated, red = 0.5 Gy, black = 2 Gy, green = 10 Gy). The predictor built with the TBI samples shows no capacity to predict the radiation status of partially irradiated mice. (B) Histogram showing association of P values for association of genes with radiation exposure. A large increase in the number of small P values close to zero is observed compared to uniform distribution in the total body irradiation group (left). No trend is evident in P values in the partial body irradiated group of genes.
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pone-0011535-g003: Prediction of radiation status of partially irradiated mice based upon the TBI gene expression profiles.(A) Diamonds represent control (non irradiated) samples, circles are exposure to AH, triangles are exposure to PH and Xs represent exposure to HL. Different dose levels were tested (blue = non-irradiated, red = 0.5 Gy, black = 2 Gy, green = 10 Gy). The predictor built with the TBI samples shows no capacity to predict the radiation status of partially irradiated mice. (B) Histogram showing association of P values for association of genes with radiation exposure. A large increase in the number of small P values close to zero is observed compared to uniform distribution in the total body irradiation group (left). No trend is evident in P values in the partial body irradiated group of genes.

Mentions: Since PB signatures of radiation injury developed from TBI-patients are currently being developed as biodosimetry assays for the screening of radiation mass casualties [9], [10], [13], [19], we sought to determine if the PB signatures generated from TBI-mice can accurately discriminate PB samples from partially irradiated mice. For this analysis, predictors of 0.5, 2, and 10 Gy developed from the PB of TBI-mice were tested against PB samples from mice exposed to 0.5, 2, or 10 Gy to AH, PH or HL. Interestingly, we found that none of the predictors of 0.5, 2, or 10 Gy irradiation generated from TBI-mice were able to predict the radiation status of partially irradiated mice at the identical dose levels from the AH, PH or HL groups (Figure 3A). Specifically, PB signatures built from TBI-mice were unable to distinguish partially irradiated mice from non-irradiated controls and could not discriminate dose levels in any animals. These results demonstrate that the total body model performs poorly in attempting to predict the radiation status of partially irradiated animals.


Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.

Meadows SK, Dressman HK, Daher P, Himburg H, Russell JL, Doan P, Chao NJ, Lucas J, Nevins JR, Chute JP - PLoS ONE (2010)

Prediction of radiation status of partially irradiated mice based upon the TBI gene expression profiles.(A) Diamonds represent control (non irradiated) samples, circles are exposure to AH, triangles are exposure to PH and Xs represent exposure to HL. Different dose levels were tested (blue = non-irradiated, red = 0.5 Gy, black = 2 Gy, green = 10 Gy). The predictor built with the TBI samples shows no capacity to predict the radiation status of partially irradiated mice. (B) Histogram showing association of P values for association of genes with radiation exposure. A large increase in the number of small P values close to zero is observed compared to uniform distribution in the total body irradiation group (left). No trend is evident in P values in the partial body irradiated group of genes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902517&req=5

pone-0011535-g003: Prediction of radiation status of partially irradiated mice based upon the TBI gene expression profiles.(A) Diamonds represent control (non irradiated) samples, circles are exposure to AH, triangles are exposure to PH and Xs represent exposure to HL. Different dose levels were tested (blue = non-irradiated, red = 0.5 Gy, black = 2 Gy, green = 10 Gy). The predictor built with the TBI samples shows no capacity to predict the radiation status of partially irradiated mice. (B) Histogram showing association of P values for association of genes with radiation exposure. A large increase in the number of small P values close to zero is observed compared to uniform distribution in the total body irradiation group (left). No trend is evident in P values in the partial body irradiated group of genes.
Mentions: Since PB signatures of radiation injury developed from TBI-patients are currently being developed as biodosimetry assays for the screening of radiation mass casualties [9], [10], [13], [19], we sought to determine if the PB signatures generated from TBI-mice can accurately discriminate PB samples from partially irradiated mice. For this analysis, predictors of 0.5, 2, and 10 Gy developed from the PB of TBI-mice were tested against PB samples from mice exposed to 0.5, 2, or 10 Gy to AH, PH or HL. Interestingly, we found that none of the predictors of 0.5, 2, or 10 Gy irradiation generated from TBI-mice were able to predict the radiation status of partially irradiated mice at the identical dose levels from the AH, PH or HL groups (Figure 3A). Specifically, PB signatures built from TBI-mice were unable to distinguish partially irradiated mice from non-irradiated controls and could not discriminate dose levels in any animals. These results demonstrate that the total body model performs poorly in attempting to predict the radiation status of partially irradiated animals.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina, United States of America.

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.

Show MeSH
Related in: MedlinePlus