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The objective of this research was to explore the dose-effect relationships of dicentric plus ring (dic + r), micronucleus (MN) and nucleoplasmic bridges (NPB) induced by carbon ions in human lymph...

In the event of radiological accidents and cancer radiotherapies in the clinic, the gastrointestinal (GI) system is vulnerable to ionizing radiation and shows GI injury. Accessible biomarkers may provide means to predict, evaluate, and treat GI tissue damage. The current study investigated radiation GI injury biomarkers in rat plasma. High-coverage targeted lipidomics was employed to profile lipidome perturbations at 72 h after 0, 1, 2, 3, 5, and 8 Gy (60Co γ-rays at 1 Gy/min) total-body irradiation in male rat jejunum. The results were correlated with previous plasma screening outcomes. In total, 93 differential metabolites and 28 linear dose-responsive metabolites were screened in the jejunum. Moreover, 52 lipid species with significant differences both in jejunum and plasma were obtained. Three lipid species with linear dose-response relationship both in jejunum and plasma were put forth, which exhibited good to excellent sensitivity and specificity in triaging different exposure levels. The linear dose-effect relationship of lipid metabolites in the jejunum and the triage performance of radiation GI injury biomarkers in plasma were studied for the first time. The present study can provide insights into expanded biomarkers of IR-mediated GI injury and minimally invasive assays for evaluation.

In order to assess the health risk of low-dose radiation to radiation professionals, monitoring is performed through chromosomal aberration analysis and micronuclei (MN) analysis. MN formation has drawbacks for monitoring in the low-dose range. Nucleoplasmic bridge (NPB) analysis, with a lower background level, has good dose-response relationships at both high and relatively low dose ranges. Dicentric and ring chromosomes were analyzed in 199 medical radiation professionals, and NPB/MN yields were analyzed in 205 radiation professionals. The effects of sex, age of donor, types of work, and length of service on these cytogenetic endpoints were also analyzed. The yields of the three cytogenetic endpoints were significantly higher in radiation professionals versus controls. Frequencies of dicentric plus ring chromosomes were affected by length of service. NPB frequencies were influenced by type of work and length of service. MN yields were affected not only by types of work and length of service but also by donor sex and age. In conclusion, dicentric plus ring chromosomes, NPB, and MN can be induced by low-dose radiation in radiation professionals. NPB is a potential biomarker to assess the health risk of occupational low-dose radiation exposure.

The objective of this research was to explore the dose-effect relationships of dicentric plus ring (dic + r), micronucleus (MN) and nucleoplasmic bridges (NPB) induced by carbon ions in human lymphocytes.Venous blood samples were collected from three healthy donors.The frequencies of dic + r, MN and NPB showed significantly increases in a dose-depended manner after exposure toThe dose-response curves of carbon ions-induced dic + r, MN and NPB were constructed. These results could be helpful to improve radiation risk assessment and dose estimation after exposed to carbon ions irradiation.

Metabolomics has great potential to process accessible biofluids through high-throughput and quantitative analysis for radiation biomarker screening. This study focused on the potential radiation responsive metabolites in rat plasma and the dose-response relationships. In the discovery stage, 20 male Sprague–Dawley rats were exposed to 0, 1, 3 and 5 Gy of cobalt-60 gamma rays at a dose rate of 1 Gy/min. Plasma samples were collected at 72 h after exposure and analyzed using liquid chromatography mass spectrometry based on non-targeted metabolomics. In the verification stage, 50 additional rats were exposed to 0, 1, 2, 3, 5 and 8 Gy of gamma rays. The concentrations of candidate metabolites were then analyzed using targeted metabolomics methods. Fifteen candidate radiation responsive metabolites were identified as potential radiation metabolite biomarkers. Metabolic pathways, such as linoleic acid metabolism and glycerophospholipid metabolism pathways, were changed after irradiation. Six radiation responsive metabolites, including LysoPC(20:2), LysoPC(20:3), PC(18:0/22:5), L-palmitoylcarnitine, N-acetylornithine and butyrylcarnitine, had good dose-response relationships ( R 2 > 0.80). The area under the curve of the panel of the 6 radiation responsive metabolites was 0.923. The radiation exposure metabolomics biomarkers and dose-response curves may have potential for rapid dose assessment and triage in nuclear and radiation accidents.

Rapid early triage and dose estimation is vital for limited medical resource allocation and treatment of a large number of the wounded after radiological accidents. Lipidomics has been utilized to delineate biofluid lipid signatures after irradiation. Here, high-coverage targeted lipidomics was employed to screen radiosensitive lipids after 0, 1, 2, 3, 5, and 8 Gy total body irradiation at 4, 24, and 72 h postirradiation in rat plasma. Ultra-performance liquid chromatography-tandem mass spectrometry with a multiple reaction monitoring method was utilized. In total, 416 individual lipids from 18 major classes were quantified and those biomarkers altered in a dose-dependent manner constituted panel A-panel D. Receiver operator characteristic curve analysis using combined lipids showed good to excellent sensitivity and specificity in triaging different radiation exposure levels (area under curve = 0.814-1.000). The equations for dose estimation were established by stepwise regression analysis for three time points. A novel strategy for radiation early triage and dose estimation was first established and validated using panels of lipids. Our study suggests that it is feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage, which can provide further insights in developing lipidomics strategies for radiation biodosimetry in humans.

Previous studies showed that the yield of cobalt-60 γ-rays-induced nucleoplasmic bridges (NPB) in human peripheral blood lymphocytes is dose dependent. However, the influence of the radiation quality and dose rates on NPB frequencies has not been investigated. The present study aimed to investigate NPB frequencies in human peripheral blood lymphocytes induced by carbon ions and explore the dose rate effect on cobalt-60 γ-rays-induced NPB. To establish dose-response curves, human peripheral blood samples were irradiated with 0, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 and 8.0 Gy of carbon ions at a dose rate of 3.0 Gy/min in vitro. To explore the dose rate effect, human peripheral blood samples were irradiated with 2.0 and 5.0 Gy of cobalt-60 γ-rays at dose rates of 0.2, 0.5, 1.0, 3.0, 5.0 and 10.0 Gy/min in vitro. NPB and micronuclei (MN) in binucleated cells were analyzed with the cytokinesis-block micronucleus cytome assay. Results showed that the dose-response curve of carbon ion-induced NPB frequencies follow a linear-quadratic model (R2 = 0.934). The relative biological effectiveness (RBE) values of carbon ions to cobalt-60 γ-rays decreased with increased NPB frequencies (ranging from 2.47 to 5.86). Compared with group 1.0 Gy/min, the NPB frequencies in groups 10.0 Gy/min (2.0 Gy), 5.0 and 10.0 Gy/min (5.0 Gy) were decreased significantly (P < 0.05). Carbon ion-induced NPB in human peripheral blood lymphocytes have a good dose-response relationship. Cobalt-60 γ-rays-induced NPB frequencies are affected by the specific dose rate.

Purpose: Simple, rapid and high-throughput dose assessment is critical for clinical diagnosis, treatment and emergency intervention in a large-scale radiological accident. The goal of this study is...

Baseline nucleoplasmic bridges (NPB) vary widely in the general population from different regions in the same country or from different countries. The baseline NPB level in the normal Chinese population and the factors affecting the baseline and radiation-induced NPB levels have not been explored yet. The cytokinesis-block micronucleus cytome assay was conducted on the peripheral blood samples of 121 healthy individuals for the baseline NPB and 52 healthy individuals for the 2 Gy γ-ray-induced NPB level. The effects of age and gender on the baseline NPB and 2 Gy γ-ray-induced NPB level were evaluated. The overall baseline NPB in the peripheral blood lymphocytes of 121 healthy adults from the general population in China was 0.46 ± 0.20 per 1000 binucleated (BN) cells. The overall baseline NPB in males (0.56 ± 0.15 per 1000 BN cells) was higher than that in females (0.36 ± 0.22 per 1000 BN cells, P

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy 60Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60Co γ-radiation.

Supplemental Material, sj-doc-1-dos-10.1177_1559325820979570 for Identification of Potential Radiation Responsive Metabolic Biomarkers in Plasma of Rats Exposed to Different Doses of Cobalt-60 Gamma Rays by Hua Zhao, Cong Xi, Mei Tian, Xue Lu, Tian-Jing Cai, Shuang Li, Xue-Lei Tian, Ling Gao, Hai-Xiang Liu, Ke-Hui Liu and Qing-Jie Liu in Dose-Response

Baseline nucleoplasmic bridges (NPB) vary widely in the general population from different regions in the same country or from different countries. The baseline NPB level in the normal Chinese population and the factors affecting the baseline and radiation-induced NPB levels have not been explored yet. The cytokinesis-block micronucleus cytome assay was conducted on the peripheral blood samples of 121 healthy individuals for the baseline NPB and 52 healthy individuals for the 2 Gy γ-ray-induced NPB level. The effects of age and gender on the baseline NPB and 2 Gy γ-ray-induced NPB level were evaluated. The overall baseline NPB in the peripheral blood lymphocytes of 121 healthy adults from the general population in China was 0.46 ± 0.20 per 1000 binucleated (BN) cells. The overall baseline NPB in males (0.56 ± 0.15 per 1000 BN cells) was higher than that in females (0.36 ± 0.22 per 1000 BN cells, P 0.05). The effect of age on the baseline NPB was not significant, except for females in the 40-year age group. The overall 2 Gy γ-ray-induced NPB frequency for male donors was lower than that for female donors (P 0.01). No evident trend of the radiation-induced NPB level with increasing age was observed for both genders. For the baseline micronucleus (MN) and radiation-induced MN levels, the effects of gender and age were confirmed. Therefore, the gender of donors affects the baseline and radiation-induced levels of NPB and MN. In addition, the effect of the age of the donors on the baseline and radiation-induced NPB levels showed no clear pattern and needed to be further investigated.

The dose effect between nucleoplasmic bridges (NPB) and relatively low doses of ionising radiation remains unknown. Accordingly, this study investigated the NPB frequencies in human peripheral blood lymphocytes exposed to low-dose (60)Co γ-rays. Complex anomalies, including fused nuclei (FUS), horse-shoe nuclei (HS) and circular nuclei (CIR), which possibly originated from multiple NPBs, were also scored. Human peripheral blood samples were collected from three healthy males and irradiated with 0-1 and 0-0.4 Gy (60)Co γ-rays. A cytokinesis-block micronucleus cytome assay was then conducted to analyse NPB, PFHC (NPB plus three complex nuclear anomalies) and micronucleus (MN) in binucleated cells. All dose-response curves followed the linear model for both NPB frequency and PFHC cell frequency. The dose-response curves between NPB frequency and absorbed dose at 0-1 and 0-0.4 Gy were y = 0.0037x + 0.0005 (R (2) = 0.979, P < 0.05) and y = 0.0043x + 0.0004 (R (2) = 0.941, P < 0.05), respectively. The dose-response curves between PFHC cell frequency and absorbed dose at 0-1 and 0-0.4 Gy were y = 0.0044x + 0.0007 (R (2) = 0.982, P < 0.05) and y = 0.0059x + 0.0005 (R (2) = 0.969, P < 0.05), respectively. The statistical significance of differences between the irradiated groups (0-0.4 Gy) and background levels of NPB, PFHC and MN were also analysed. The lowest analysable doses of NPB, PFHC and MN were 0.12, 0.08 and 0.08 Gy, respectively. In conclusion, NPBs and PFHC positively correlated with the absorbed radiation at a relatively low dose.