Plasma Proteins As Biodosimetric Markers of Low-Dose Radiation in Mice

Abstract

Long-term exposures to low-dose radiation (LDR) may trigger several specific biological responses, including dysregulation of the immune and inflammatory systems. Here, we examined whether biodosimetry of LDR can be used to protect tissues from radiation or assess cancer risk. Mice were subjected to gamma-irradiation with repeated or single-dose LDR, and then the organ indices, peripheral hemogram, and blood biochemistry were analyzed. An antibody array was applied followed by enzyme-linked immunosorbent assay to evaluate the utility of multiple plasma proteins as biomarkers of repeated LDR in a murine model. LDR induced inapparent symptoms but slight variations in peripheral blood cell counts and alterations in blood biochemical indicator levels. Specific plasma proteins in the LDR groups were altered in response to a higher dose of irradiation at the same time points or a single-dose equivalent to the same total dose. Plasma levels of interleukin (IL)-5, IL-12p40, P-selectin, and serum amyloid A1 were associated with the LDR dose and thus may be useful as dosimetric predictors of LDR in mice. Estimating the levels of certain plasma proteins may yield promising biodosimetry parameters to accurately identify individuals exposed to LDR, facilitating risk assessment of long-term LDR exposure in individuals.

Keywords: biodosimetry; biomarkers; low-dose radiation; plasma protein.

Figure 1.

Changes in murine peripheral blood count after low-dose radiation (LDR). Peripheral blood counts of (A) white blood cells (WBC), (B) lymphocytes (LYM), (C) red blood cells (RBC), and (D) platelets (PLT) at 24 h after the last irradiation dose. Data are presented as the mean ± SEM. n = 10, *P < 0.05, **P < 0.01. NC, normal control.

Figure 2.

Blood biochemistry analysis in mice after low-dose radiation (LDR). (A) Alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) alkaline phosphatase (ALP), (D) creatine kinase (CK), (E) urea (UREA), and (F) cholesterol (CHOL). Data are presented as the mean ± SEM. n = 5, *P < 0.05, **P < 0.01. NC, normal control.

Figure 3.

Comparison of plasma protein levels before and after low-dose irradiation (LDR) using an antibody array. (A) Heatmap of plasma protein expression between non-radiation control and low-dose radiation groups is shown. The heatmap was drawn using MultiExperiment Viewer (4.9.0). (B) Violin plot shows Avery expression levels of total analyzed proteins in each group. (C) Venny analysis indicated that the common plasma proteins were differentially altered between pre-irradiation and post-irradiation samples in all LDR groups. (D) Protein-protein interaction network of differentially altered proteins from the common set of LDR groups is shown. (E) Expression of selected plasma proteins from the antibody array in each LDR group. Data are expressed as the mean ± SEM. n = 3, *P < 0.05, **P < 0.01, ***P < 0.001. NC, normal control.

Figure 4.

Plasma protein levels in mice in response to low-dose radiation (LDR), determined by ELISA. A, Interleukin (IL)-5, (B) IL-12p40, (C) P-selectin (SELP), (D) IL-10, (E) matrix metalloproteinase 14 (MMP14), (F) serum amyloid A (SAA1). Data are expressed as the mean ± SEM; n = 6-8 mice for each group. *P < 0.05, **P < 0.05, ***P < 0.05, ****P < 0.0001. NC, normal control.

Figure 5.

Plasma protein expression levels in mice were altered in response to a fraction of low-dose radiation (LDR). (A) Interleukin (IL)-5, (B) IL-12p40, (C) P-selectin (SELP), (D) IL-10, (E) matrix metalloproteinase 14 (MMP14), and (F) serum amyloid A (SAA1). Data are expressed as the mean ± SEM; n = 6-8 mice for each group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. NC, normal control.