PURPOSE:Ionizing radiation-induced intestinal injury (RIII) is a significant complication of radiotherapy and nuclear radiation incidents. Mitochondria, the centers of energy metabolism and apoptosis, are pivotal in the pathogenesis of RIII. Under irradiation conditions, multiple mitochondrial function-related genes modulate the production of reactive oxygen species and ATP, maintain mitochondrial DNA, induce mitophagy, and activate the apoptotic pathway associated with mitochondrial dysfunction, leading to intestinal tissue injury. Mitochondrial function-related genes are pivotal in maintaining the normal function of mitochondria and moderate RIII. This review summarizes the mechanisms of mitochondrial function-related genes in RIII and potential therapeutic strategies, aiming to provide references for further research on RIII and clinical prevention and treatment. CONCLUSION:Mitochondrial dysfunction driven by the dysregulation of genes related to mitochondrial function (nuclear genes and mitochondrial genome) is a key mechanism of RIII pathogenesis. At present, research on pivotal regulators remains limited, necessitating deeper investigation with multi-omics approaches. Precisely targeting these mitochondrial function-related genes offers a promising therapeutic strategy for reducing mitochondrial damage and treating RIII.

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:Radiation-induced intestinal injury (RIII) is a common adverse reaction of pelvic radiotherapy. There is no effective treatment method yet. Intestinal stem cells (ISCs) can differentiate into various intestinal cell types. ISCs play an indispensable role in intestinal repair and functional reconstruction after RIII. This review focuses on the effects of radiation on ISCs, their influencing factors, changes in related signaling pathways following radiation, and potential therapeutic targets. The aim is to provide a theoretical basis and new research direction for studying mechanisms and targeted intervention strategies for RIII. METHOD:A comprehensive literature search was conducted in PubMed, Web of Science for studies published from 2010 to 2025. The search strategy combined keywords and controlled vocabulary terms related to ionizing radiation, intestinal stem cells, injury/repair mechanisms. CONCLUSION:The injury and repair of ISCs are precisely regulated by signaling pathways such as Wnt, Notch, BMP, and EGF, and depend on support from the intestinal stem cell niche. Factors such as radiation dose rate, age, sex, and diet also significantly influence the radiation response of ISCs. This review summarizes the factors and regulatory pathways that influence ISC damage induced by ionizing radiation and explains potential mechanisms. It offers a direction for future research on preventing and controlling RIII through ISCs.

BACKGROUND:Radiation-induced intestinal injury (RIII) is a serious complication of radiotherapy and is closely associated with mitochondrial dysfunction, but the underlying mechanism remains unclear. METHODS:Mitochondria‑related differentially expressed genes (DEGs) were identified using online databases in an RIII model. Histopathological staining analysis was performed to evaluate injury severity. The expression of Mrm2 was examined in vivo after irradiation. RESULTS:The core functional modules of the identified DEGs included mitochondrial‑coding genes and apoptosis‑related genes. Histopathological analysis showed that RIII aggravated significantly in a dose‑ and time‑dependent manner. Notably, Mrm2 was continuously upregulated after irradiation in vivo. CONCLUSION:Mrm2 may serve as a key regulatory factor mediating mitochondrial dysfunction in radiation‑induced intestinal injury.

PURPOSE:Radiation-induced intestinal injury (RIII) is a common complication after radiotherapy for abdominal and pelvic tumors, which seriously affects the prognosis and treatment outcome of patients, and lacks effective prevention and treatment methods. The primary pathological manifestations of RIII are the death of intestinal epithelial cells, as well as the destruction of the intestinal mechanical barrier's integrity, which is closely related to various kinds of programmed cell death (PCD). In addition, radiation-induced DNA double-strand breaks can trigger a variety of PCDs. Elucidating how different PCD pathways regulate RIII molecular mechanisms and identifying the key therapeutic targets will provide the theoretical foundation for developing RIII prevention and treatment strategies. This review systematically expounds the role of PCD in the pathogenesis of RIII and summarizes the relevant small molecule drugs currently under research. CONCLUSION:PCD plays a central role in the occurrence and development of RIII. Analyzing single pathways and elucidating the 'cross-talk' and regulatory logic between different forms of PCD, as well as identifying key molecular targets located at the intersection of multiple pathways, is likely to become a more effective new direction for prevention and treatment.

OBJECTIVE:To establish and validate a dose-response curve for dicentric chromosomes (DC) induced by X-rays in human peripheral blood in vitro using semi-automated scoring. METHODS:Peripheral blood samples were collected from three healthy individuals and exposed to X-ray doses of 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 5 Gy at a dose rate of 1.158 Gy/min. Dicentric chromosomes in metaphase were scored both full- and semi-automatically, and a dose-response curve was generated with CABAS software based on dicentric yields. Dose estimations were then performed for 12 biodosimetry standard samples and one sample from a patient with X-ray-induced skin injury. RESULTS:Dicentric yields increased with X-ray doses from 0 to 5 Gy (r = 0.943, P < 0.01). The dose-response association followed a linear-quadratic model: Y = 0.0002 (± 0.0001) + 0.0379 (± 0.0032) × D + 0.0253 (± 0.0014) × D2 (R2 = 0.998, P < 0.01), where Y represents dicentric yields and D is the dose. The estimated dose for 12 validation samples aligned closely with actual doses. The estimated whole-body average absorbed dose for the patient was 0.73 Gy, with observed DC over-dispersion suggesting partial body exposure. By using the Dolphin model, this dose was refined to 2.22 Gy and estimated irradiated body volume was 35.94%, consistent with clinical diagnosis. CONCLUSIONS:The dose-response curve developed using semi-automated scoring offer a reliable and efficient approach for dose estimation and clinical diagnosis in nuclear radiation emergencies. It could also support retrospective biodosimetry of partial-body, non-uniform radiation exposure.

In the event of nuclear accidents and incidents,when emergency resources are scarce,rapid and high-throughput biodosimeters for massive population triage and estimation are essential to guide medical treatment. Lymphocyte dynamics,chromosome aberration analysis,and micronucleus assays are mainly used to estimate the biological dose of radiation[1]. However,these technologies require highly trained personnel to perform and interpret and have the limitations of time consumption and low throughput,underscoring the urgent need for the development of radiation biomarkers and early classification. Dose and temporal responses as well as efficient triage models are important facets of radiation biodosimeters.

OBJECTIVE:This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells. METHODS:Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43. RESULTS:Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure. CONCLUSION:Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

Bioinformatics has become increasingly integral to radiation biology, also known as radiobiology, providing substantial support through data storage, conversion, visualization, and sharing. This review aims to deepen understanding of bioinformatics application in radiobiology by introducing key databases and analytical tools in radiobiology, including general bioinformatics databases, radiobiology-specific databases, data processing tools, and statistical analysis tools for differentially expressed genes (DEGs) and LC/MS analysis. This review also discusses bioinformatics applications in radiobiological fields, such as radioresistance and immune cell enrichment. Despite these advances, challenges such as data interoperability remain. Methods and projects to address these issues, such as GeCo and GMQL, are also examined.

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.

PURPOSE:In the event of a large-scale radiological accident, rapid and high-throughput biodosimetry is the most vital basis in medical resource allocation for the prompt treatment of victims. However, the current biodosimeter is yet to be rapid and high-throughput. Studies have shown that ionizing radiation modulates expressions of circular RNAs (circRNAs) in healthy human cell lines and tumor tissue. circRNA expressions can be quantified rapidly and high-throughput. However, whether circRNAs are suitable for early radiation dose classification remains unclear. METHODS:We employed transcriptome sequencing and bioinformatics analysis to screen for radiation-differentially expressed circRNAs in the human lymphoblastoid cell line AHH-1 at 4 h following exposure to 0, 2, and 5 Gy 60Co γ-rays. The dose-response relationships between differentially expressed circRNA expressions and absorbed doses were investigated using real-time polymerase chain reaction and linear regression analysis at 4 h, 24 h, and 48 h post-exposure to 0, 2, 4, 6, and 8 Gy. Six distinct dose classification models of circRNA panels were established and validated by receiver operating characteristic (ROC) curve analysis. RESULTS:A total of 11 radiation-differentially expressed circRNAs were identified and validated. Based on dose-response effects, those circRNAs changed in a dose-responsive or dose-dependent manner were combined into panels A through F at 4 h, 24 h, and 48 h post-irradiation. ROC curve analysis showed that panels A through C had the potential to effectively classify exposed and non-exposed conditions, which area under the curve (AUC) of these three panels were all 1.000, and the associate p values were .009. Panels D through F excellently distinguished between different dose groups (AUC = 0.963-1.000, p < .05). The validation assay showed that panels A through F demonstrated consistent excellence in sensitivity and specificity in dose classification. CONCLUSIONS:Ionizing radiation can indeed modulate the circRNA expression profile in the human lymphoblastoid cell line AHH-1. The differentially expressed circRNAs exhibit the potential for rapid and high-throughput dose classification.

Purpose: UVB exposure accelerates skin aging and age-associated pigmentation, but their relationship remains unclear. UVB induces premature senescence and melanin production within melanocytes, accompanied by the up-regulation of p53 and cellular tyrosinase (TYR). As a tumor suppressor gene, p53 can keep the genome intact by modulating cell apoptosis and growth arrest during DNA injury. P53 also relates to age-associated pigmentation, directly or indirectly regulating pigment-related gene expression. Melatonin effectively regulates tyrosinase activity and resists aging. This study focused on the regulation of p53 on TYR to understand the association between premature senescence and senescence-associated pigmentation and determine the mechanism behind melatonin affecting UVB stimulated melanin production.Methods: Primary melanocytes were extracted and identified from the male foreskin. The primary melanocytes were transduced using lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR to knock down TYR expression. The melanin content was determined using the NaOH method, the oxidation of 3,4-Dihydroxy-L-phenylalanine (L-DOPA) into dopachrome to determine TYR activity, and Western blotting was used to detect the level of TYR protein. After being pretreated with Nutlin-3 or PFT-α to up or down-regulate p53 levels or melatonin for 12 h, primary melanocytes were under UVB irradiation at 80 mJ/cm2. The senescence-associated beta-galactosidase (SA-β-gal) kit analyzed premature senescence. At the same time, the level of p53, p-p53, and TYR protein were detected using the automated capillary electrophoresis western analysis in melanocytes at 72 h after UVB irradiation. Wild-type and TYR (–/–) or TYR (+/–) knockout C57BL/6J mice were used to verify the regulatory role of TYR on melanin synthesis in vivo . Moreover, the effect of melatonin on skin erythema and pigmentation induced by UVB irradiation was illustrated in vivo.Results: Primary melanocytes showed a deep black color after L-DOPA staining, higher TYR protein, and mRNA expression. Tyrosinase activity and melanin levels induced by UVB irradiation were significantly alleviated after being infected with pLKD-CMV-EGFP-2A-Puro-U6-TYR (P <0.05). Premature senescence, tyrosinase activity, and melanin levels were increased under UVB irradiation induction. Furthermore, there was a dramatic increase following the Nutlin-3 treatment while significantly inhibited after being treated with PFT-α (P <0.05) in the primary melanocytes. Melatonin inhibited UVB-induced premature senescence, associated with decreased p53 level and phosphorylation on serine-15 position, decreased UVB-induced tyrosinase activity and melanin levels, and reduced TYR expression. TYR (–/–) knockout mice were recognized through white hair colors, whiskers, paws, and pigment loss in the eyes. The tyrosinase activity and melanin levels in the whiskers follicles of TYR (–/–) knockout mice were also significantly decreased (P <0.05) relative to the wild-type (WT) counterparts. Skin erythema and melanin pigmentation induced by UVB irradiation were reduced in the dorsal and ear skin of C57BL/6J mice topically pretreated with 2.5% melatonin.Conclusion: Melanin synthesis induced by UVB irradiation is dependent on TYR in primary melanocytes and C57BL/6J mice. Moreover, p53 links the UVB irradiation-induced premature senescence and senescence-associated pigmentation in the primary melanocytes, and directly regulates TYR in primary mel

PurposeIonizing radiation (IR)-induced transcriptional changes are considered a potential biodosimetry for dose evaluation and health risk monitoring of acute or chronic radiation exposure. It is crucial to understand the impact of confounding factors on the radiation-responsive gene expressions for accurate and reproducible dose assessment. This study aims to explore the potential influence of exposures to chemotherapeutic agents such as cyclophosphamide (CP) and mitomycin C (MMC) on IR-induced transcriptional biomarkers.MethodsThe human B lymphoblastoid cells (AHH-1) were exposed to 0, 20, 50, 100, 200 and 500 & mu;g/ml CP or 0, 0.025, 0.05, 0.1 and 1 & mu;g/ml MMC, respectively. The appropriate concentrations of CP and MMC were added for 1 h before irradiation with 0, 2, 4 and 6 Gy of Co-60 & gamma;-rays at a dose rate of 1 Gy/min. Cell viability was evaluated by CCK-8 assay. The gene expression responses of 18 radiation-induced transcriptional biomarkers were examined at 24 h after exposures to CP and MMC, respectively. The expression levels of five crucial DNA interstrand crosslinks (ICLs) repair genes were also evaluated. The biodosimetry models were established based on the specific radiation-responsive gene combinations.ResultsThe baseline transcriptional levels of the 18 selected genes were slightly affected by CP treatment in the absence of IR, while the transcript responses to IR could be inhibited as the concentration of CP up to 50 & mu;g/ml. MMC treatment up-regulated the background levels in most radiation-responsive gene expressions. Of 18 genes, only the relative mRNA expression levels of CDKN1A and BBC3 were repressed after treatment with IR and MMC in combination. The relative mRNA level of RAD51 was significantly up-regulated after exposure to CP, while the expression of FANCD2, RAD51 and BLM showed an overall increase in response to MMC treatment. After irradiation, the relative mRNA expression levels of FANCD2, BRCA2 and RAD51 exhibited dose-dependent increases in IR alone and MMC treatment groups. In addition, the biodosimetry models were established using 2-4 radiation-responsive genes based on different radiation exposure scenarios.ConclusionOur findings suggested that IR-induced gene expression changes were slightly affected after exposure to a relatively low concentration of CP and MMC. Gene expression combinations might improve the broad applicability of transcriptional biodosimetry across diverse radiation exposures.

Objective:To study the influence of circular RNA hsa_circZDHHC21_004 on the proliferation of human small intestinal epithelial cells HIEC-6 after 60Co γ-rays exposure. Methods:HIEC-6 cells were exposed to 60Co γ-rays at 0, 5, 10, and 15 Gy with a dose rate of 1 Gy/min. The expression level of hsa_circZDHHC21_004 in the irradiated HIEC-6 cell was detected. Hsa_circZDHHC21_004 was knocked-down to investigate the influences of hsa_circZDHHC21_004 on the proliferation of irradiated HIEC-6 cells by CCK-8 assay and colony formation assay. Results:The expression level of hsa_circZDHHC21_004 in HIEC-6 cells was upregulated by (1.00±0.24), (1.34±0.28), (1.85±0.31), and (2.80±0.64) times of control after 0, 5, 10, and 15 Gy irradiation, respectively and there were significant difference between 10 or 15 Gy group and 0 Gy group ( F=10.86, P=0.008). Knockdown of hsa_circZDHHC21_004 significantly increased the proliferation rate of HIEC-6 cells at 24, 48, and 72 h after 10 Gy irradiation compared with non-irradiated control ( t=-6.25, -5.83, -7.75, P < 0.001). Under 2 and 5 Gy irradiation, the clone formation rates of the hsa_circZDHHC21_004 knockdown cells were significantly higher than those of the control ( t=-7.45, -8.83, P<0.01). Conclusions:Hsa_circZDHHC21_004 is increased after irradiation and influenced the proliferation of irradiated HIEC-6 cells.

Eye lens opacification (cataract) induced by ionizing radiation is an important concern for radiation protection. Human lens epithelial cells (HLE-B3) were irradiated with gamma-rays and radiation effects, including cell prolifer-ation, cell migration, cell cycle distribution, and other changes related to the beta-catenin pathway, were deter-mined after 8-72 h and 7 d. In an in vivo model, mice were irradiated; DNA damage (?H2AX foci) in the cell nucleus of the anterior capsule of the lens was detected within 1 h, and radiation effects on the anterior and posterior lens capsules were observed after 3 months. Low-dose ionizing radiation promoted cell proliferation and migration. The expression levels of beta-catenin, cyclin D1, and c-Myc were significantly increased in HLE-B3 cells after irradiation and beta-catenin was translocated into the cell nucleus (activation of the Wnt/beta-catenin pathway). In C57BL/6 J mouse lens, even a very low irradiation dose (0.05 Gy) induced the formation of gamma H2AX foci, 1 h after irradiation. At 3 months, migratory cells were found in the posterior capsule; expression of beta-catenin was increased and it was clustered at the nucleus in the epithelial cells of the lens anterior capsule. The Wnt/beta-catenin signaling pathway may an important role in promoting abnormal proliferation and migration of lens epithelial cells after low-dose irradiation.

ABSTRACT:Quantification of gamma-H2AX foci can estimate exposure to ionizing radiation. Most nuclear and radiation accidents are partial-body irradiation, and the doses estimated using the total-body irradiation dose estimation formula are often lower than the actual dose. To evaluate the dose-response relation of gamma-H2AX foci in human peripheral blood lymphocytes after partial-body irradiation and establish a simple and high throughput model to estimate partial-body irradiation dose, we collected human peripheral blood and irradiated with 0-, 0.5-, 1-, 2-, 3-, 4-, 5-, 6-, and 8-Gy gamma rays to simulate total-body irradiation in vitro. Gamma-H2AX foci were quantitated by flow cytometry at 1 h after irradiation, and a dose-response curve was established for total-body irradiation dose estimation. Then, a partial-body irradiation dose-response calibration curve was established by adding calibration coefficients based on the Dolphin method. To reflect the data distribution of all doses more realistically, the partial-body irradiation dose-response calibration curve was divided into two sections. In addition, partial-body irradiation was simulated in vitro, and the PBI data were substituted into curves to verify the accuracy of the two partial-body irradiation calibration curves. Results showed that the dose estimation variations were all less than 30% except the 25% partial-body irradiation group at 1 Gy, and the partial-body irradiation calibration dose-response curves were YF 1 = - 3.444 x 2 + 18.532 x + 3.109, R 2 = 0.92 (YF ≤ 27.95); YF 2 = - 2.704 x 2 + 37.97 x - 56.45, R 2 = 0.86 (YF > 27.95). Results also suggested that the partial-body irradiation dose-response calibration curve based on the gamma-H2AX foci quantification in human peripheral blood lymphocytes is a simple and high throughput model to assess partial-body irradiation dose.

People who exposed to low-dose ionizing radiation chronically could have an increased risk of lens opacity. It is very important to clarify the mechanism of lens opacity induced by low-dose ionizing radiation for the prevention and early intervention of cataract. This paper describes the experiments that human lens epithelial cells SRA01/04 were irradiated with 0.2 Gy 137 Cs and 2 Gy 60 Co γ-rays. Differentially expressed mRNAs were screened by gene chip technology at 48 h after irradiation, 3 690, 3 304, and 3 970 differentially expressed genes were identified in 0.2 Gy vs 2 Gy, 0.2 Gy vs 0 Gy, 2 Gy vs 0 Gy groups respectively. Bioinformatic analysis showed that the majority of these genes are associated with oxidative phosphorylation, cell proliferation and adhesion pathways. The expression of genes（PIM1, HMGB1, BRE, JUN） related to cell proliferation in SRA01/04 and HLE-B3 cells were verified by real-time PCR at 24 h and 48 h after different doses of γ-rays. The results showed that in both cell lines, the expression levels of PIM1, HMGB1, and BRE at most low-dose irradiated groups were significantly higher than those in the non-irradiated group at 24 h after irradiation, and still showed an increasing trend at 48 h after irradiation. However, at 48 h after 2 Gy irradiation, gene expression levels decreased significantly or returned to baseline. The results showed that low-dose ionizing radiation induces significant alterations of mRNAs expression in human lens epithelial cells, the differentially expressed genes play some roles in series of important biological processes and functional pathways, which could be useful to reveal molecular mechanisms of low-dose ionizing radiation induced lens opacification or cataract.

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.

电离辐射会对人体造成损伤,根据受照剂量、时间等因素的不同可诱发多种生物效应.目前对于低剂量辐射产生的健康效应仍有争议,筛选对低剂量敏感的辐射响应生物标志物,对于完善低剂量辐射生物效应机制、拓宽低剂量辐射在临床中的应用均具有重要理论意义.综述探讨各核糖核酸(RNA)在低剂量辐射反应中的变化及其对辐射敏感性的调节作用,同时评估各RNA作为低剂量辐射响应标志物的潜力.