Association between single nucleotide polymorphism of DNA damage repair related genes and radiosensitivity in healthy individuals.

Radiosensitivity in humans can influence radiation-induced normal tissue toxicity. As radiosensitivity has a genetic predisposition, we aimed to investigate the possible association between four single nucleotide polymorphism (SNP) sites and the radiosensitivity in healthy people. We genotyped four selected SNPs: TRIP12 (rs13018957), UIMC1 (rs1700490) and POLN (rs2022302), and analyzed the association between SNP and the radiosensitivity in healthy people. We distinguished radiosensitivity by chromosome aberration analysis in healthy individuals. Healthy donors were classified into three groups based on chromosomal aberrations: resistant, normal and sensitive. Using the normal group as a reference, the genotypes CT and CC of rs13018957 (CT: OR = 26.13; CC: OR = 15.97), AA of rs1700490 (OR = 32.22) and AG of rs2022302 (OR = 13.98) were risk factors for radiosensitivity. The outcomes of the present study suggest that four SNPs are associated with radiosensitivity. This study lends insights to the underlying mechanisms of radiosensitivity and improves our ability to identify radiosensitive individuals.

Effects of Neutron and Gamma Rays Combined Irradiation on the Transcriptional Profile of Human Peripheral Blood.

We studied the effects of neutrons, neutrons and γ rays, and γ rays exposures on the transcription spectrum in human peripheral blood of three healthy adult men. Samples were irradiated with 1.42 Gy 2.5-MeV neutrons, 0.71 Gy neutrons and 0.71 Gy 137Cs γ rays, and 1.42 Gy 137Cs γ rays. Transcriptome sequencing identified 56 differentially co-expressed genes and enriched 26 KEGG pathways. There are 97, 45 and 30 differentially expressed genes in neutron, neutron and γ ray combined treatment, and γ rays, respectively, and 21, 3 and 8 KEGG pathways with significant differences are enriched. Fluorescence quantitative polymerase chain reaction (qPCR) verified differential co-expression of AEN, BAX, DDB2, FDXR, and MDM2. Additionally, irradiation of AHH-1 human lymphocytes with a 252Cf neutron source at 0, 0.14, 0.35, and 0.71 Gy, fluorescence qPCR revealed a dose-response relationship for BAX, DDB2, and FDXR at dose ranges of 0-0.71 Gy, with R2 of 0.803, 0.999, and 0.999, respectively. Thus, neutrons can induce more differentially expressed genes and enrich more pathways. Combined treatment of neutrons and γ-rays may incorporate damage of both high and low LET, the genes activated by neutrons and γ rays combined are almost the combination of genes activated by neutron and γ rays combined treatment. BAX, DDB2 and FDXR are differentially expressed after irradiation by Deuterium-Deuterium (D-D) neutron source and 252Cf neutron source, so they are expected to be molecular targets of neutron damage.

ESTABLISHMENT OF THE IN VITRO DOSE-RESPONSE CALIBRATION CURVE FOR X-RAY-INDUCED MICRONUCLEI IN HUMAN LYMPHOCYTES.

The cytokinesis-block micronucleus assay has proven to be a reliable technique for biological dosimetry. This study aimed to establish the dose-response curve for X-ray-induced micronucleus. Peripheral blood samples from three healthy donors were irradiated with various doses and scoring criteria by the micronuclei (MN) in binucleated cells. The results showed that the frequency of MN increased with the elevation of radiation dose. CABAS and Dose Estimate software were used to fit the MN and dose into a linear quadratic model, and the results were compared. The linear and quadratic coefficients obtained by the two software were basically the same and were comparable with published curves of similar radiation quality and dose rates by other studies. The dose-response curve established in this study can be used as an alternative method for in vitro dose reconstruction and provides a reliable tool for biological dosimetry in accidental or occupational radiation exposures.

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation.

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners' serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion.

Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity. We found that expression of 8 genes was upregulated after LDR, while expression of 5 genes was downregulated. After HDR, 54 genes were upregulated and 3 genes were downregulated, including genes related to Th1, Th2 and Th3/Tr1 cellular subtypes, Th1/Th2-type immune response genes and transcription factor-related genes. In the foregoing results, LDR and HDR in the thymus induced opposite patterns of expression for Th1-, Th2- and Th3-type related cytokines TGF-ß, C/EBP-ß and TNF-α. We also found that expression of Interferon-γ (IFN-γ) and Interleukin-2 (IL-2), which have a moderating effect on immune function, was upregulated after LDR. Furthermore, the secretion of negative regulatory factors Interleukin-1ß (IL-1ß), Interleukin-4 (IL-4), transforming growth factor-ß (TGF-ß) and Interleukin-21 (IL-21) was reduced after LDR, but HDR produced the opposite effect and stimulated their expression. These findings suggest that LDR may induce a Th1-type immune response, while HDR may lead to a Th2-type immune response.

Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

BACKGROUND: Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. OBJECTIVE: The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. METHODS: Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. RESULTS: HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. CONCLUSION: These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.