PURPOSE:Gene expression analysis provides a minimally invasive approach for biological dosimetry. To advance point-of-care applications, this study aimed to establish and validate an improved gene expression biodosimetry system by employing an expanded panel of radiation-responsive genes in human peripheral blood. METHODS:Human B lymphoblastoid cells (AHH-1) and peripheral blood from 10 healthy donors were irradiated with 60Co γ-rays at doses of 0, 1, 2, 4, 6, and 8 Gy (dose rate: 1 Gy/min). The expression patterns of four candidate transcriptional biomarkers (ZMAT3, SESN1, AEN, and TRIAP1) and a panel of radiation-responsive genes were characterized at 6-48 h post-irradiation. The impact of different dose rates (0.2, 1, and 2 Gy/min) on these gene expressions was also investigated. For each gene, calibration curves were established by fitting a linear regression between the logarithm of absorbed dose and ΔCt values. Gene selection and model construction were performed using stepwise regression to obtain optimized multi-gene models. The accuracy of these dosimetry models for dose prediction was validated in independent ex vivo and in vivo cohorts. RESULTS:The four candidate genes exhibited robust, dose-dependent expression from 6 to 48 h post-irradiation, independent of dose-rate variations (0.2-2 Gy/min). Most genes in the expanded panel, including the candidates, showed strong linear relationships between log2 of dose and ΔCt values across all time points when the 0 Gy point was excluded from regression (R2 > 0.90, S < 0.50). Based on these validated genes, optimized multi-gene models achieved high predictive accuracy (R2 = 0.81-0.89) with fewer genes. Furthermore, these improved models demonstrated accurate dose estimation capabilities when validated with both ex vivo- and in vivo-irradiated peripheral blood samples. CONCLUSIONS:Our study expanded the panel of reliable radiation biomarkers and developed optimized multi-gene models for accurate dose estimation, thereby advancing the standardization and practicality of gene expression biodosimetry.

PURPOSE:Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification. METHODS:Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed. RESULTS:In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model. CONCLUSION:This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship.

Objective:To explore the characteristics of lipid metabolism in rat plasma after total body irradiation(TBI) in order to provide scientific evidence of radiation biomarkers.Methods:For the non-targeted lipidomics study, 50 SD rats were divided into 6 groups and irradiated with 0, 1, 2, 3, 5 or 8 Gy 60Co γ-rays, respectively. For the targeted lipidomics study, 25 rats were divided into 5 groups and irradiated with 0, 0.5, 2.5, 4 or 6 Gy. Venous blood samples were collected and plasma were separated 4 h after TBI. Radiation-sensitive lipids were screened and their concentrations were determined. Receiver operating characteristic curve (ROC) and dose-response were analyzed. Results:A total of 15 radiation differential lipids were screened out based on non-targeted lipidomics study and 7 of them were identified as radiosensitive lipids by targeted lipidomics analysis. The ROC of radiosensitive lipids distinguished area under curve (AUC) of samples in 0 Gy group and > 0 Gy group, < 2 Gy group and ≥ 2 Gy group were all > 0.75. The AUC values were increased to 0.96 and 0.94 after the panel of radiation sensitive lipids ROC analysis. The concentrations of LysoPC(18: 2), LysoPC(22: 0), PC(18: 0/18: 2), PE(18: 2/16: 0) and PE(18: 2/18: 0) decreased with irradiation dose within 0-6 Gy.Conclusions:A total of 7 plasma radiosensitive lipids in rat plasma were identified 4 h after TBI, and the panel of them could be used for specific dose classification. Five of the lipids had good dose-response relationship.

The intestinal compensatory proliferative potential is a key influencing factor for susceptibility to radiation-induced intestinal injury. Studies indicated that the carnitine palmitoyltransferase 1 (CPT1) mediated fatty acid β-oxidation (FAO) plays a crucial role in promoting the survival and proliferation of tumor cells. Here, we aimed to explore the effect of 60Co gamma rays on CPT1 mediated FAO in the radiation-induced intestinal injury models, and investigate the role of CPT1 mediated FAO in the survival and proliferation of intestinal cells after irradiation. We detected the changed of FAO in the plasma and small intestine of Sprague Dawley (SD) rats at 24 h after 60Co gamma irradiation (0, 5 and 10 Gy), using target metabolomics, qRT-PCR, immunohistochemistry (IHC), western blot (WB) and related enzymatic activity kits. We then analyzed the FAO changes in radiation-induced intestinal injury models regardless of ex vivo (mice enteroids), or in vitro (normal human intestinal epithelial cell lines, HIEC-6). HIEC-6 cells were transduced with lentivirus vector GV392 and treated with puromycin for obtaining CPT1 stable knockout cell lines, named CPT1 KO. CPT1 enzymatic activities of HIEC-6 cells and mice enteroids were also inhibited by pharmaceutical inhibitor ST1326 and Etomoxir (ETO), to study the function of CPT1 in the survival and proliferation of HIEC-6 cells after 60Co gamma irradiation. We found that CPT1 mediated FAO was altered in the small intestine of the SD rats after irradiation, especially, the expression level and enzymatic activity of CPT1 were significantly increased. Similarly, the expression levels of CPT1 were also remarkably enhanced in mice enteroids and HIEC-6 cells after irradiation. CPT1 inhibition decreased the proliferation of the HIEC-6 cells and mice enteroids after irradiation partially by reducing the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways activation, CPT1 inhibition also reduced the proliferation of mice enteroids after irradiation partially by down-regulating the Wnt/β-catenin signaling activity. In conclusion, our study indicated that CPT1 plays a crucial role in promoting intestinal epithelial cell proliferation after irradiation.

Plenty of reports focus on the effects of low-dose radiation (LDR) on peripheral blood lymphocytes in radiation workers. However, studies on red blood cells (RBCs) in radiation workers are rarely reported. Many studies focused on investigate the hemogram of radiation staffs without detecting other components of RBCs. To explore the potential effect of LDR on RBCs, we detected the level of RBC count, hemoglobin, 2,3-disphosphoglycerate (2,3-DPG), and glutathione (GSH), and then analyzed the factors on these indices in 106 medical radiation workers. As a result, RBC count was affected by sex, age, type of work, length of service (only for females), and annual effective dose (only for males). Hemoglobin status was affected by sex, type of work, and annual effective dose (only for males). Sex, age, and type of work had no effects on the concentration of 2,3-DPG and GSH. Length of service affected 2,3-DPG concentration, and annual effective dose affected GSH level. In conclusion, chronic occupational LDR exposure may have an effect on RBC count, hemoglobin status, and the concentration of 2,3-DPG and GSH in radiation workers to some extent. However, it is still unknown how this kind of influence affects the health of radiation workers.

Objective:To investigate the changes of CPT1A and CPT1B protein expression in rat intestinal epithelial cells (IEC-6) after 60Co γ-ray irradiation, and the mechanism of the influence of carnitine palmitoyltransferase 1 (CPT1) on the proliferation of irradiated IEC-6 cells. Methods:IEC-6 cells were cultured in serum-normal medium or in serum-starved medium overnight, and pretreated with 20 μmol/L palmitic acid (PA) before irradiation with 0, 5, 10, and 15 Gy. At 24 h after irradiation, the cellular protein was collected for the measurement of CPT1A and CPT1B proteins by Western blot. The influences of ETO, an inhibitor of CPT1, on the survival and proliferation of irradiated IEC-6 cells were analyzed by colony formation assay and CCK-8 assay. The protein expressions and phosphorylation levels of the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in 5 Gy irradiated IEC-6 cells pre-treated with ETO were analyzed by Western blot at 48 h after radiation.Results:When IEC-6 cells were cultured in serum-normal medium together with PA, the protein level of CPT1A was significantly increased after 15 Gy irradiation ( t=-2.82, P<0.05). When IEC-6 cells were cultured in serum-starved medium, the protein level of CPT1A was significantly increased at 5, 10, and 15 Gy ( t=-3.28, -8.72, -8.67, P<0.05). When IEC-6 cells were cultured in serum-starved medium together with PA, the protein levels of CPT1A were significantly increased at 5, 10 and 15 Gy ( t=-10.69, -7.02, -8.23, P<0.05), the protein levels of CPT1B were significantly increased at 10 and 15 Gy ( t=-3.73, -5.05, P<0.05). After irradiation, the survival and proliferation of IEC-6 cells in ETO group were significantly lower than those in control group ( t=5.46, 13.22, P<0.05), and the protein level of ERK1/2 and p-JNK in ETO group were significantly lower than those in control group ( t=4.01, 3.29, 10.68, 14.44, P<0.05). Conclusions:CPT1 promoted radiation-induced IEC-6 injury cells survival and proliferation by enhancing the expression level of ERK1/2 protein and the activity of JNK.

Introduction 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. Material and methods High-coverage targeted lipidomics was employed to profile lipidome perturbations at 72 h after 0, 1, 2, 3, 5, and 8 Gy (Co-60 gamma-rays at 1 Gy/min) total-body irradiation in male rat jejunum. The results were correlated with previous plasma screening outcomes. Results 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. Discussion 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. Conclusion The present study can provide insights into expanded biomarkers of IR-mediated GI injury and minimally invasive assays for evaluation.

Objective This study aims to analyze the alteration of carnitine profile in the small intestine of abdominal irradiation-induced intestinal injury rats and explore the possible reason for the altered carnitine profile. Methods The abdomens of 15 male Sprague Dawley (SD) rats were irradiated with 0, 10, and 15 Gy of 60 Co gamma rays. The carnitine profile in the small intestine and plasma samples of SD rats at 72 h after abdominal irradiated with 0 Gy or 10 Gy of 60 Co gamma rays were measured by targeted metabolomics. The changes of fatty acid β-oxidation (FAO), including the expression of carnitine palmitoyltransferase 1 (CPT1) and acyl-CoA dehydrogenases, were analyzed in the small intestine samples of SD rats after exposed to 0, 10, and 15 Gy groups. Results There were eleven acylcarnitines in the small intestine and fourteen acylcarnitines in the plasma of the rat model significantly enhanced, respectively (P < .05). The expression level and activity of CPT1 in the small intestine were remarkably increased (P < .05), and the activity of acyl-CoA dehydrogenase in the small intestine was noticeably reduced (P < .01) after abdominal irradiation. Conclusion The enhanced acylcarnitine levels in the small intestine of abdominal irradiation rats might relate to the FAO pathway disequilibration.

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.

目的:探索年龄、性别因素对我国健康人群外周血淋巴细胞核质桥自发率的影响,为核质桥的影响因素研究提供科学依据.方法:选取98例健康成人,其中男性52例,女性46例,年龄范围为20～68岁,平均年龄为(40.7±12.6)岁.按年龄分为20～29岁组(22人)、30～39岁组(23人)、40～49岁组(25人)和50岁以上组(28人).抽取研究对象外周血2 mL,采用胞质分裂阻滞法培养细胞40 h后,加入松胞素B(终浓度为10μg/mL),继续培养至68 h收获细胞.每个受试者观察1000个双核细胞,分析核质桥、微核及核芽的数量.结果:核质桥总体自发率为每个细胞0.56‰,男性略高于女性,但差异无统计学意义(P>0.05).男性在不同年龄组间,核质桥自发率差异无统计学意义(P>0.05).女性40～49岁年龄组核质桥自发率最高,显著高于20～29岁组(U=2.31,P<0.05).微核自发率女性高于男性(U=4.40,P<0.05),男性和女性受试者40～49岁组微核自发率均为最高.核芽自发率在不同性别间的差异无统计学意义(P>0.05),在不同年龄组间无明显变化规律.结论:健康人群中的核质桥自发率较低,不受性别因素影响,在20～49岁范围内具有随年龄增加而升高的趋势.

Objective:To screen radiosensitive lipid metabolites in rat small intestine and analyze their metabolic pathways, in order to provide scientific basis for radiation enteropathy biomarkers.Methods:The total body irradiation of 60Co γ rays was performed to rats with different doses of 0, 1, 2, 3, 5 and 8 Gy. The changes of lipids in small intestine were studied by targeted lipidomics method based on liquid chromatography coupled mass spectrometry (LC-MS). Results:Fifteen lipids in small intestine were screened as radiosensitive metabolites at 3 d after irradiation, including 4 up-regulated lipids and 11 down-regulated lipids( t=-6.395, 5.998, 5.836, -5.503, -5.449, -5.422, 4.841, 4.802, 4.621, 4.457, 4.426, 4.373, 4.110, 3.945, 3.902, P< 0.05 and FDR < 0.05). The metabolic pathways of sphingolipid, glycerophosphoplipid were significantly enriched. Four phosphatidyl serines (PS)increased while 1 phosphatidic acid(PA), 2 sphingomyelins(SM) and 4 fatty acids(FA)decreased in a good dose-response manner( R2> 0.80, P< 0.05), which were more potential radiation enteropathy biomarkers. Conclusions:Lipid metabolites in rat small intestine were significantly changed after the rat was total body irradiated with 60Co γ-rays.Eleven lipids with good dose-response relationship were more potential to be radiation enteropathy biomarkers.

Objective:To explore the feasibility of the optimized cytokinesis-block (CB) assay on radiation-induced nucleoplasmic bridge (NPB), and to provide a scientific basis for the application of NPB in biological dose estimation.Methods:Human peripheral blood in vitro was irradiated with 2 Gy 60Co γ-rays at a dose rate of 1 Gy/min (0 Gy control group). According to the culture time after irradiation, blood samples were divided into group 48, 56, 68 and 72 h. Cytochalasin-B (Cyt-B) with a concentration of 6 μg/ml was added into the samples at 28 h and harvested at 48, 56, 68 and 72 h after irradiation, respectively. On the other hand, the blood samples were treated with different concentration of Cyt-B i. e., 0.6, 1, 2, 6 and 10 μg/ml at the beginning of culture (0 h) and harvested at 68 h after irradiation. The proportion of mononucleated, binucleated and multinucleated cells, radiation-induced NPB and micronucleus (MN) frequencies were analyzed. Results:The nuclear division index (NDI) and proportion of binucleated cells at 2 Gy and 0 Gy had tendency of increasing with cell culture time. NPB frequencies (0.023 0-0.033 0/cell) and MN frequencies had no significantly difference ( P> 0.05). With the increase of Cyt-B concentration, NDI and the proportion of binucleated cells in group 2 Gy and 0 Gy also increased, but NPB frequencies (0.023 0-0.047 0/cell) had no significant difference ( P> 0.05). MN frequencies of group 10 μg/ml were significantly lower than that of group 6 μg/ml ( U=2.74, P< 0.01). Conclusions:Cell culture time and Cyt-B concentration had no significant influence on radiation-induced NPB frequencies, suggesting that NPB could be obtained by appropriately reducing cell culture time and Cyt-B could be added into blood samples at the beginning of culture. But this protocol reduced the number of cells for further analysis, and thus its feasibility for dose estimation still need to be studied.

Purpose 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. Materials and methods Venous blood samples were collected from three healthy donors. C-12(6+) ions beam was used to irradiate the blood samples at the energy of 330 MeV and linear energy transfer (LET) of 50 keV/mu m with a dose rate of 1 Gy/min in the spread-out Bragg peak. The irradiated doses were 0 (sham irradiation), 1, 2, 3, 4, 5 and 6 Gy. Dic + r chromosomes aberrations were scored in metaphases. The cytokinesis-block micronucleus cytome (CBMN) was conducted to analyze MN and NPB. The maximum low-dose relative biological effectiveness (RBEM) values of the induction of dic + r, MN and NPB in human lymphocytes for C-12(6+) ions irradiation was calculated relative to Co-60 gamma-rays. Results The frequencies of dic + r, MN and NPB showed significantly increases in a dose-depended manner after exposure to C-12(6+) ions. The distributions of dic + r and MN exhibited overdispersion, while the distribution of NPB agreed with Poisson distribution at all doses. Linear-quadratic equations were established based on the frequencies of dic + r and MN. The dose-response curves of NPB frequencies followed a linear model. The derived RBEM values for dic + r, MN and NPB in human lymphocytes irradiated with C-12(6+) ions were 8.07 +/- 2.73, 2.69 +/- 0.20 and 4.00 +/- 2.69 in comparison with Co-60 gamma-rays. Conclusion The 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.

目的:探讨利用人外周血淋巴细胞微核分析估算局部照射剂量的可行性.方法:收集2例人外周血样本,每例血样分为两部分,一部分不照射,另一部分再分成两组分别于1和5 Gy的60Coγ射线下离体照射,剂量率为1 Gy/min.将来自同一样本的照射血与未照射血按1:3或3:1比例混合以模拟局部照射,共分析8组混合血样中双核淋巴细胞微核(MN)率,利用国际原子能机构(IAEA)推荐的Dolphin's模型推算混合血中受照血的微核率,并采用卫生行业标准(WS/T 178—1999)推荐的剂量效应曲线估算局部照射剂量.结果:各组混合血样MN分布均不符合泊松分布.1 Gy照射组估算的局部剂量与实际照射剂量偏差较大,5 Gy照射组估算的局部剂量与实际照射剂量较接近.结论:离体情况下,MN能较好的用于估算局部照射剂量,且MN可能更适用于较高剂量的估算.

Objective:To investigate the metabolite changes in rat plasma after total body irradiation (TBI) and to explore dose classification based on radiation sensitive metabolites.Methods:The differential metabolites induced by radiation were screened and verified by metabolomics. In the discovery stage, 50 SD rats were irradiated with 0, 1, 2, 3, 5 and 8 Gy of 60Co γ-rays. In the verification stage, 25 rats were irradiated with 0, 0.5, 2.5, 4 and 6 Gy. Peripheral blood samples were collected 4 h after irradiation, and plasma was separated. Radiation-induced differential metabolites were identified and their concentrations were determined. Receiver operating characteristic (ROC) curve of the differential metabolites was used to classify dose range. Results:In the discovery stage, 8 radiation-induced differential metabolites in rat plasma were identified and four of them (cytosine, L-hexylcarnitine, Linoelaidylcarnitine and L-palmitylcarnitine) were upregulated, which was confirmed in the verification stage. The area under the curve (AUC) for the specific dose was >0.75. After combining these four metabolites, the AUC value to classify the radiation dose of 0 Gy versus >0 Gy, <2 Gy versus ≥2 Gy, <5 Gy versus ≥5 Gy were 0.96, 1 and 0.94, respectively.Conclusions:The metabolites in rat plasma changed significantly at 4 h after TBI, where 8 differential metabolites were identified. Cytosine, L-hexylcarnitine, linoelaidylcarnitine and L-palmiylcarnitine were stably over-expressed in the plasma after irradiation. The combination of these four compounds had high classification accuracy and thus may applicable as radiation sensitive biomarkers for dose classification.

Objective:To screen the indicators of retrospective dose estimation, based on 5 cytogenetic methods to assess the victim followed-up at 4 year after 192Ir radiation accident in Nanjing. Methods:The chromosome aberration (dic + r) assay, cytokinesis block micronucleus (MN) and nucleoplasmic bridge (NPB) assay, fluorescence in situ hybridization (FISH)-based and G banding-based translocation analysis were used to retrospective biological dose estimation. Results:The estimated doses of FISH-based and G banding -based analysis were 1.45 and 1.21 Gy respectively, which was similar to the biological dose estimated short time after the accident. However, the estimated doses by chromosome aberration, micronucleus and nucleoplasmic bridge method were 0.56, 0.45 and 0.41 Gy respectively, which were lower than the corresponding biodose. Correction factors were used to adjust the biodose.Conclusions:In the 4th years after exposure, the estimated biological doses by FISH-based and G banding-based translocation were consistent with the biodose.Therefore, the two methods were suitable for retrospective dose estimation, while correction factors should be considered in chromosome aberration method for retrospective dose estimation.

Objective:To explore the effects of ultraviolet B (UVB) on the premature senescence of human immortalized keratinocytes HaCaT cells and the possible underlying molecular mechanism.Methods:HaCaT cells were exposed with UVB of different doses (20, 50, 80 and 100 mJ/cm 2). At 72 h after exposure, cellular morphology was observed by Giemsa staining, cell proliferation was detected by clone formation assay, and the proportion of premature senescence cells was detected by β-galactosidase staining. The number change of lysosomes was detected by Lyso-Tracker Red fluorescence probe at 24, 48 and 72 h after exposure. Cell migration was measured by scratch test at 24 h and 48 h after exposure. The protein expressions of p53 and p16 related to premature senescence were detected by Western blot assay at 72 h after exposure. Results:After UVB exposure, HaCaT cells showed a premature senescence phenotype. At 72 h after exposure, the cell volume increased ( F=115.18, P<0.05), the cell proliferation ability decreased ( F=410.32, P<0.05), the activity of β-galactosidase increased ( F=16.31, P<0.05), and the expressions of P53 and P16 increased. In addition, the number of lysosomes increased at 24, 48, and 72 h after exposure ( F=17.65, 38.36, 13.66, P<0.05), and cell migration capacity was inhibited at 24 and 48 h after exposure ( F=8.21, 11.48, P<0.05). Conclusions:UVB exposure can induce premature senescence of HaCaT cells by increasing the expression of p53 and p16 proteins.

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.

To explore whether a computed tomography (CT) examination of the head and neck region induces biological damage and whether the damage was correlated with the radiation dose. Peripheral blood was taken from 33 individuals who received head and neck CT examinations. Blood samples were divided into three groups: the control group and the in vivo and in vitro irradiation groups. The number of DNA double-strand breaks was estimated by comparing the changes in the rates of γ-H2AX foci formation in the peripheral blood before and after CT examination. The absorbed dose and effective dose were calculated with the software VirtualDose based on the Monte Carlo method, and the absorbed doses in blood were estimated accordingly. The γ-H2AX foci rates were increased in the in vivo (p < 0.001) and in vitro irradiation groups (p < 0.001) after CT examination when compared with those in the control group. The rate of γ-H2AX foci formation showed linear dose–responses for the CT dose index volume (CTDIvol), dose–length product (DLP), and blood dose after CT examination. A CT examination of the head and neck region provides a high enough radiation dose to induce DNA double-strand breaks in cells in the peripheral blood. There was a linear correlation between the formation of DNA double-strand breaks and radiation doses after CT examination. In addition to ensuring image quality, in a real clinical situation, the scanning area should be strictly administered, and repeated operations should be avoided to minimise the patient’s radiation dose.

Objective:To screen radiosensitive lipid metabolites in rat plasma and analyze their metabolic pathways in order to provide scientific basis for radiation damage biomarker.Methods:The whole body irradiation of 60Co γ rays was performed to rats with different doses of 0, 1, 3 and 5 Gy. The changes of lipids in plasma were detected by untargeted lipidomics method based on liquid chromatography coupled mass spectrometry. Results:Twenty plasma lipids were identified as the potential radiosensitive biomarkers at 7 days after irradiation, including 13 over-expressed lipids and 7 down-expressed lipids, where 12 lipids well responded to radiation doses.Conclusions:Lipid metabolites in rat plasma are significantly changed after exposure to γ rays, and the metabolic pathways of sphingolipid, glycerophospholipid and glycosylphosphatidylinositol (GPI) are significantly enriched.