Research progress in biological effects of low-dose radiation / 中国辐射卫生

The biological effects of low-dose radiation (LDR) are still a research hotspot in the field of radiobiology. As research deepens on LDR-induced biological effects and the mechanisms, growing evidence shows that LDR produces distinct biological effects from high-dose radiation, which questions the linear non-threshold model. This article reviews LDR-induced bystander effect, hormesis, adaptive response, and hyper-radiosensitivity, as well as the mechanisms, in order to provide a reference for the transformation of basic research on LDR-related biological effects to clinical application.

Ultra-low-dose chest computed tomography without anesthesia in the assessment of pediatric pulmonary diseases / Tomografia computadorizada de tórax de ultrabaixa dosagem sem anestesia naavaliação de doenças pulmonares pediátricas

Abstract Objective To evaluate the feasibility of using ultra-low-dose computed tomography of the chest with iterative reconstruction without anesthesia for assessment of pulmonary diseases in children. Methods This prospective study enrolled 86 consecutive pediatric patients (ranging from 1 month to 18 years) that underwent ultra-low-dose computed tomography due to suspicion of pulmonary diseases, without anesthesia and contrast. Parameters used were: 80 kVp; 15-30 mA; acquisition time, 0.5 s; and pitch, 1.375. The adaptive statistical iterative reconstruction technique was used. Subjective visual evaluation and quantitative assessment of image quality were done using a 5-point scale in 12 different structures of the chest. Results Mean age was 66 months (interquartile range, 16-147). Final diagnosis was performed in all exams, and 44 (51.2%) were diagnosed with cystic fibrosis, 27 (31.4%) with bronchiolitis obliterans, and 15 (17.4%) with congenital pulmonary airways malformations. Diagnostic quality was achieved in 98.9%, of which 82.6% were considered excellent and 16.3% were slightly blurred but did not interfere with image evaluation. Only one case (1.2%) presented moderate blurring that slightly compromised the image, and previous examinations demonstrated findings compatible with bronchiolitis obliterans. Mean effective radiation dose was 0.39 ± 0.15 mSv. Percentages of images with motion artifacts were 0.3% for cystic fibrosis, 1.3% for bronchiolitis obliterans, and 1.1% for congenital pulmonary airways malformations. Conclusion Chest ultra-low-dose computed tomography without sedation or anesthesia delivering a sub-millisievert dose can provide image quality to allow identification of common pulmonary anatomy and diseases.

Resumo Objetivo Avaliar a viabilidade do uso de tomografia computadorizada com ultrabaixa dose com reconstrução iterativa sem anestesia para avaliação de doenças pulmonares em crianças. Métodos Este estudo prospectivo envolveu 86 pacientes pediátricos consecutivos (um mês a 18 anos) submetidos à tomografia computadorizada com ultrabaixa dose por suspeita de doenças pulmonares, sem anestesia e contraste. Os parâmetros utilizados foram: 80 kVp; 15-30 mA; tempo de aquisição, 0,5 s; e pitch de 1,375. Foi utilizada a técnica de reconstrução estatística adaptativa iterativa. A avaliação visual subjetiva e a avaliação quantitativa da qualidade da imagem foram feitas com uma escala de 5 pontos em 12 estruturas do tórax. Resultados A média de idade foi de 66 meses (intervalo interquartil, 16-147). O diagnóstico final foi feito em todos os exames e 44 (51,2%) foram diagnosticados com fibrose cística, 27 (31,4%) com bronquiolite obliterante e 15 (17,4%) com malformação congênita pulmonar das vias aéreas. A qualidade diagnóstica foi alcançada em 98,9% dos casos, dos quais 82,6% foram considerados excelentes e 16,3% alteração leve na definição, mas isso não interferiu na avaliação da imagem. Apenas um caso (1,2%) apresentou alteração moderada na definição, comprometeu discretamente a imagem, e exames prévios demonstraram achados compatíveis com bronquiolite obliterante. A dose de radiação média efetiva foi de 0,39 ± 0,15 mSv. As porcentagens de imagens com artefatos de movimento foram de 0,3% para fibrose cística, 1,3% para bronquiolite obliterante e 1,1% para malformação congênita pulmonar das vias aéreas. Conclusão É possível realizar a tomografia computadorizada com ultrabaixa dose torácica sem sedação ou anestesia, administrando uma dose de submilisievert, com qualidade de imagem suficiente para a identificação pulmonar anatômica e de doenças pulmonares comuns.

Effect of Cimetidine on the Histopathology and the Expression of SOD2 and GPX1 in Low-dose Accumulative Irradiated Beagle Dogs Spleen / 中国药学杂志

OBJECTIVE: To study the effect of cimetidine on the histopathology and the expression of SOD2, GPX1 gene and protein in low-dose accumulative irradiated Beagle dogs spleen and to investigate the mechanism of cimetidine′s protective effect on low-dose accumulative irradiation. METHODS: Twenty-four male Beagle dogs were divided into six groups: normal control group,model group,positive drug control group and cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 respectively. The dogs were irradiated with 60Co-γ-ray at 0.040 8 mGy•min-1 rate for 23 d. Cimitidine was administered intragastrically during irradiation, once a day. Microscope was adopted to observe the pathologic change of spleen and the expression levels of SOD2,GPX1 gene and protein in the spleen tissue of dogs were detected by qRT-PCR and immunohistochemistry techniques. RESULTS: Compared with the model group,cimetidine ameliorated the pathological changes and ultrastructure lesions in the spleen of dogs. Also compared with the model group, the levels of SOD2 and GPX1 protein in cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 were higher(P<0.05) and the levels of SOD2 and GPX1 mRNA of the three cimetidine groups were increased significantly(P<0.01). CONCLUSION: Cimetidine can reduce the histological damage. Cimetidine can upregulate the expressions of SOD2 and GPX1 gene and protein and it has good protective effect on the antioxidant system injury.

Comparison of radiation exposure by area before and after emergency center remodeling

OBJECTIVE: Radiation is used extensively in emergency centers. Computed tomography and X-ray imaging are used frequently. Portable X-rays, in particular, cause a significant amount of indirect radiation exposure to medical personnel. The authors' emergency center was remodeled, and a comparative study of radiation exposure was carried out in certain places that had experienced radiation for a long time. METHODS: The cumulative radiation dose was measured 20 times in the 24 hours prior to remodeling, and the cumulative radiation dose was measured again 20 times across the 24-hour period. The measurement points were fixed at the emergency doctor's seat (Zone A), charge nurse's seat (Zone B), and section nurse's seat (Zone C). During the 24-hour cumulative radiation measurement period, the number of portable X-ray shots was recorded in the emergency center. RESULTS: The mean of the 24-hour cumulative radiation measurements in zone A was 3.36±0.07 µSV and 4.54±0.07 µSV before and after remodeling, respectively (P<0.001). Regarding the number of portable X-rays performed during the measurement, a higher number of trials in the Pearson correction correlated with a higher radiation measurement. CONCLUSION: In an emergency medical center, there is a higher level of low-dose radiation exposure compared to that experienced from natural radioactivity. Regarding the number of portable X-rays, the cumulative radiation dose measured 24 hours after remodeling increased and can be assumed to be related to the environment.

Low-dose radiation and Alzheimer's disease: Neuronal effects and a potential modality for therapy? / 中华放射医学与防护杂志

Exposure to low-dose radiation (LDR,mostly less than 100 mGy) may reduce the vulnerability of exposed tissues to subsequent high-dose radiation (HDR)-induced damage,a phenomenon known as adaptive responses,which occurs via mechanisms including anti-inflammation and anti-oxidation.Alzheimer's disease (AD) is a type of dementia that causes problems with memory,thinking,and behavior.Using the available literature,this review will examine whether there is any effect of LDR on AD.The available evidence shows that although LDR can alter the expression of some genes related to AD such as Apbb1,Lrp1,and Il1α,these alterations do not cause AD-like syndromes in animals,suggesting that LDR may also simultaneously upregulate several protective mechanisms that prevent the eventual development of AD.Furthermore,LDR seems capable of improving the symptoms of AD,as evidenced by the experience of an 81-year-old female AD patient.This patient was diagnosed with AD more than 10 years ago and gradually progressed to advanced AD in 2015,despite routine treatment.The patient then received about 12 computed tomography scans (about 40 mGy each) up until Nov.2017,which significantly improved her quality of life and reduced several AD symptoms.The improvement in this patient's medical condition led to a few recent clinical trials investigating the effects of LDR on AD.To date,there is no efficient therapy available for AD,thus whether exposure to LDR at 100 mGy can provide a preventive or therapeutic effect for AD is an important issue.If LDR is a potential treatment for AD,as suggested by this reported case,this non-invasive approach would also bear the merit that it would be unlikely to cause a significant radiation health risk,as the LDR could be delivered locally to the head without any impact on other organs.

Expressions of ire1α and xbp1 mRNA and proteins in mouse testis cells induced by low dose ionizing radiation / 吉林大学学报(医学版)

Objective: To detect the expressions of inositol-requiring enzyme-1α (IRE1α) and X box-binding protein-1 (XBP1) mRNA and proteins in mouse testis cells, and to explore the role of IRE1-XBP1 pathway activation in the endoplasmic reticulum stress induced by low dose radiation (LDR) in the mouse testis cells. Methods: A total of 50 heatly male ICR mice were randomly divided into 10 groups. After the mice were irradiated with 75 mGy X-ray in whole body at different time (0, 3, 6, 12, and 24 h) or with different doses (0, 50, 75, 100, and 200 mGy) of X-ray fori2 h, the expression levels of IRElα, T-XBP1 and S-XBP1 mRNA and proteins were measured by real-time quantitative PCR and Western blotting method, respectively. Results: The expression levels of IRElα, T-XBP1 and S-XBP1 mRNA (except T-XBP1 and S-XBP1 mRNA at 3 h after irradiation) in the testis cells of the mice after irradiated with 75 mGy X-ray for 0-24 h were increased with the time prolongation, and reached to the maximum value at 6 h after irradiation, then were gradually decreased. Compared with 0 h group, the expression levels of IRElα mRNA (6, 12, and 24 h after irradiation), T-XBP1 mRNA and S-XBP1 mRNA (6 and 12 h after irradiation) were significantly increased (P<0. 05 or P<0. 01); the expression intensities of IRElα and S-XBP1 proteins were increased; the expression intensities of IRE1α (6 and 12 h after irradiation) and S-XBP1 (24 h after irradiation) proteins were increased most significantly, but the expression intensity of T-XBP1 protein was slightly decreased. The expression levels of IRE1α, T-XBP1 and S-XBP1 mRNA in the testis cells of the mice after irradiated with 0-200 mGy for 12 h were increased, and reached to the maximum values after 75 mGy irradiation, then they were gradually decreased, even below 0 mGy. Compared with 0 mGy group, the expression levels of IRE1α mRNA in the testis cells of the mice in 75 and 200 mGy groups and the expression levels of T-XBP1 mRNA and S-XBP1 mRNA in 75 mGy group were significantly increased (P<0. 05 or P<0. 01); the expression intensities of IREla protein in 75 mGy group and S-XBP1 protein in 75 and 200 mGy groups were increased mostly, while the expression intensity of T-XBP1 protein had no obvious change. Conclusion: LDR can induce the increase of IRE1α and S-XBP1 mRNAs and proteins, and activate the IRE1-XBP1 pathway in endoplasmic reticulum stress.

Preliminary research on telomere length of residents in high level natural background radiation area Yangjiang of China / 中华放射医学与防护杂志

Objective To explore the effect of long-term low dose ionizing radiation on telomere length in adults. Methods Forty female residents aged more than 55 years old from high level natural background radiation area in Yangjiang city and forty age-matched female residents from control area in Enping city were selected by quota sampling as high background group and control group, respectively. Genomic DNA was isolated from their peripheral blood. Telomere length was determined using real time q-PCR. The t-test was used to compare the square roots of the means of two groups. The individuals were divided into four groups based on ages ( 55 -, 60 -, 65 - and ≥70 ) and four groups based on BMI ( <18. 5, 18. 5-23. 99, 24. 0 -27. 99 and ≥28. 0). After adjusting age and BMI, multivariate linear regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. The individuals were divided into longer telomere length group (≥2 ) and shorter telomere length group ( <2). Logistic regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. Results The average cumulative dose was(169. 52 ± 27. 43)mSv for high background group and(47. 52 ± 6. 50)mSv for control group. The telomere length of high background group was( 1. 98 ± 1. 25 ) , shorter than that of control group ( 2. 69 ± 1. 44 ) with statis-tically significant difference(t=2. 24, P <0. 05). The multivariate linear regression analysis revealed that the effect of cumulative dose on telomere length was not significant ( P>0. 05 ) . Association between telomere length and cumulative dose was explored through Logistic regression, and odds ratio was taken as 0. 992(95% CI, 0. 985-0. 999 ) . There was a weak inverse association between telomere length and cumulative dose, because the odds ratio ( OR) was very close to 1. Conclusions No obvious dose-effect relationship between telomere length of residents and cumulative radiation doses was found. But the long-term low dose ionizing radiation may lead to the shortening of the telomere length in adults.

MicroRNA expressions in peripheral blood plasma of the residents from high background radiation area of Yangjiang, China / 中华放射医学与防护杂志

Objective To explore the effects of high background radiation on the expressions of miR-16, miR-106b, miR-449a, miR-34a and let-7g in peripheral blood plasma of the residents .Methods Totally 110 healthy female long-term local residents aged over 50 years were randomly selected from the high background radiation area and the control area , while their age, body mass index(BMI) and other indicators were surveyed .The relative expression levels of miRNAs in peripheral blood plasma of these women were quantitatively detected by real-time fluorescence quantitative PCR ( RT-PCR) .Then t-test was used to analyze the cumulative dose , age and BMI between the high background and control group .Mann-Whitney U-test was used for statistical analysis of miRNA expression levels between two groups , and the multiple regression analysis was used finally .Results Compared with the control group , the cumulative dose of individuals in the high background group was about four times higher (t=42.803, P0.05).Conclusions miR-16 and miR-106b may serve as biomarkers for the early stage of low dose radiation health effects .

A study on cancer mortality of the residents in the high background radiation area in Yangjiang,China (1979-2002) / 中华放射医学与防护杂志

Objective To increase the statistic power to estimate radiation-induced cancer risk on the basis of analysis of the 1999-2002 follow-up data from high background radiation areas (HBRA), in combination with those in the period 1979-1998, and further to estimate radiation-induced cancer risk at low dose after adjustment of individual smoking factor.Methods Cohort studies were conducted of cancer mortality for the residents in both HBRA and control area (CA), with follow-up made in phases.The present study was first focused on the collection of cancer mortality data during 1999-2002, with preliminary analysis of the risks of cancer mortality.And then, the effort was dedicated to analysis of both the risks of cancer mortality and the smoker-adjusted risks of radiation-induced cancer mortality from for the residents in HBRA in period 1999-2002 based on the pooled data during 1999-2002 and 1979-1998 through ID record linkage.Person-years were estimated using Epicure/DATAB model.The relative risk (RR), the excess relative risk coefficient (ERR/Sv) and confidence interval (CI) of cancer mortality from 1979 to 2002 were estimated using Poisson regress model in AMFIT mode.Results A total of 76 264 persons in HBRA and CA was followed up during 1999-2002, covering 300 523 person-years and 2 267 deaths identified, including 239 cancer deaths.Based on pooled data, 125 079 persons were followed up during 1979-2002, which covered 2 293 463 person-years and 14 711 deaths identified, including 1 441 died of cancer.The sex-and age-adjusted RR of all cancers in the HBRA during 1979-2002 was 0.99 (95％ CI: 0.89 to 1.11), showing no statistically significant differences between HBRA and CA (P ＞ 0.05).The value of ERR/Sv of all cancer mortality during 1979-2002 was-0.01 (95％ CI:-0.50 to 0.64).Smoker-adjusted RR of all cancer mortality in HBRA during 1987-2002 was 1.00 (95％ CI:0.87 to 1.15), with no statistically significant difference (P ＞ 0.05).The value of ERR/Sv for all cancers during 1987-2002 was 0.01 (95％ CI:-0.56 to 0.81) after adjustment of smoking.Conclusions Increased risk was not found in relation to radiation exposure at low dose in HBRA.After adjustment of smoking, the statistical difference has not been shown in all cancer mortality between HBRA and CA, but excess relative risk increased slightly.

Effect of ATM on low-dose hyper-radiosensitivity in A549 cells synchronized at G2 phase / 中华放射肿瘤学杂志

Objective To investigate the low-dose hyper-radiosensitivity (HRS)/induced radioresistance (IRR) in A549 cells synchronized at G2 phase and the role of ATM kinase in the process.Methods Human lung adenocarcinoma cell line A549 was synchronized at G2 phase by aphidicolin.The ATM-specific activator and inhibitor,chloroquine and KU55933,were used to regulate the activity of ATM.The colony formation assay was used to evaluate cell survival.Flow cytometry was used to determine the cell cycle of radiation-exposed A549 cells synchronized at G2 phase.Immunofluorescence was used to observe the dynamics of γ-H2AX fluorescence and evaluate the efficiency of DNA repair in A549 cells synchronized at G2 phase.Western blot was used to detect the expression of phosphorylated ATM (Ser1981) and ATM.Results A549 cells synchronized at G2 phase had substantially enhanced HRS than non-synchronized cells.The dose-induced transition from HRS to 1RR was in accordance with the dose-response pattern of early G2/M checkpoint.However,with the same threshold dose,the activation of early checkpoint occurred earlier and lasted longer than normal.The activation of ATM kinase inhibited HRS and enhanced DNA repair,while the inhibition of ATM kinase enhanced HRS and hindered DNA repair.Conclusions ATM kinase-mediated early G2+M checkpoint is a molecular switch for HRS in synchronized A549 cells.Low-dose irradiation with G2-phase synchronization and ATM inhibitor can enhance the low-dose radiosensitivity.

Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation.

Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

BACKGROUND: We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. OBJECTIVE: We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. METHODS: To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. RESULTS: Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. CONCLUSION: These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation.

The cancer risks of medical radiation exposure associated mainly with CT scans / 日本プライマリ・ケア連合学会誌

Japan has experienced serious nuclear disaster being a country hit by atomic bombs and as well as the occurrence of recent nuclear plant accidents. On the other hand, the Japanese population is exposed to higher dose of medical radiation compared to other developed countries, which is due to increasing number of diagnostic computed tomography (CT) examinations. The correlation between low-dose radiation exposure and cancer risks has been discussed nationwide since Fukushima nuclear plant accident has occurred, whereas cancer risks due to low-dose ionizing radiation from CT scans have been evident in recent large cohort studies. Though CT scan is a valuable diagnostic tool in medical practice because of its high resolution image with speed of scanning, it is crucial to evaluate whether the use of CT is appropriate weighing the benefits and possible risks. Hospitalist is required to have core competency to improve quality of medical care of the hospital and to coordinate with other departments or co-medical workers. In this regard, we discuss how hospitalist could play a role to justify the use of CT and minimize unnecessary radiological exposure, cooperating with radiologists or radiological technologists.

The effects of low dose radiation on the levels of oxidative damage and antioxidant in population of high background radiation area of Guangdong / 中华放射医学与防护杂志

Objective To investigate the effects of low dose radiation on the level of oxidative damage and antioxidant in population of high background radiation area of Guangdong.Methods A total of 48 male residents who lived in high background radiation area(HBRA) of Guangdong province and 48 male residents who lived in neighboring Enping control area were chosen as the objectives and control respectively.The peripheral venous blood of two groups was collected,and then the levels of 8-OHdG and TrxR were determined by enzyme linked immunosorbent assay (ELISA).Results Compared with the CA group [(315.39 ± 100.59) ng/ml],the level of 8-OHdG [(272.64 ± 96.85) ng/ml] decreased significantly in HBRA (t =2.121,P ＜0.05).Compared with the CA group [(0.467 ±0.056) ng/ml],the level of TrxR [(0.496 ± 0.044) ng/ml] increased significantly in HBRA (t =-2.823,P ＜ 0.05).The results of multiple linear regression analysis demonstrated that the chronic exposure to low dose of radiation had significant effects on the expression level of 8-OHdG and TrxR (t =-2.327,2.367,P ＜ 0.05) after adjustment for confounding factors such as age,drinking,tea drinking,smoking,medical exposure and stressful events.Conclusions Chronic exposure to low dose radiation may decrease the level of oxidative and enhance the level of antioxidant.

Mitochondrial modulation of apoptosis induced by low-dose radiation in mouse testicular cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells.</p><p><b>METHODS</b>Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase (T-NOS) and Na+/K+ ATPase activities were biochemically assayed. Reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) were quantified by real-time reverse-transcription PCR (RT-PCR). Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry.</p><p><b>RESULTS</b>LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na+/K+ ATPase activity and mitochondrial Δψm, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes.</p><p><b>CONCLUSION</b>LDR can induce testicular cell apoptosis through mitochondrial signaling pathways.</p>

Prevention and rehabilitation of Shengxue Pills on mice injured by low-dose radiation and their mechanisms / 中草药

Objective: To study the prevention and rehabilitation of Shengxue Pills on liver, spleen, bone marrow cells, peripheral blood lymphocyte of mice injured by low-dose radiation and their mechanisms. Methods: Mice were randomly divided into five groups: control, Shengxue Pills prevention, Shengxue Pills rehabilitation, model 1 (corresponding to rehabilitation), and model 2 (corresponding to prevention) groups. Using the ELISA method to detect the activity of hydroxyl radical, superoxide anion radical, and ornithine decarboxylase (ODC) in liver and spleen cells. The bone marrow cells and peripheral lymphocyte micronucleus rate were observed under high power lens. Results: Compared with control group, the amounts of hydroxyl radical and superoxide anion radical in the two model groups were obviously increased. Compared with the corresponding model groups, the above indexes in prevention group and rehabilitation group were significantly decreased. Compared with the control group, the activity of ODC in mice of the two model groups was obviously enhanced, but bone marrow cells and peripheral lymphocyte micronucleus rate were increased. Compared with the corresponding model groups, the activity of ODC in mice of prevention and rehabilitation groups was weakened, and bone marrow cells and peripheral lymphocyte micronucleus rate were decreased. But each index of spleen cells showed no significant difference. Conclusion: Shengxue Pills could effectively prevent and rehabilitate the damage in liver cells, peripheral blood lymphocytes, and bone marrow cells of mice injured by low-dose radiation.

Genome-wide DNA methylation changes induced by low dose radiation in mouse / 中华放射医学与防护杂志

Objective To study the whole genome DNA methylation changes induced by low dose radiation (LDR) in mouse,and mRNA expression profiles of DNMT1 and MBD2 in peripheral blood mononuclear cell (PBMC) and tissues.Methods Thirty male BALB/c mice were randomly divided into 3 groups:control,single exposure (0.5 Gy),and fractionated exposure of 6 MV X-rays for 10 d (0.05 Gy/d × 10 d).Control mice were sham-treated.To determine the immediate (early) effect of irradiation,15 mice (5/group) were sacrificed 2 h after the last irradiation.The other 15 mice were sacrificed 1 month after the last irradiation (delayed effect).Before sacrifice,blood was sampled immediately.Kidney,liver,spleen,brain and lung tissues were collected.A global DNA methylation quantification Kit and highperformance liquid chromatography (HPLC) were used to investigate the methylation level in blood DNA.The expressions of DNMT1 and MBD2 were determined by RT-PCR.Results For the early effects of irradiation,as compared with controls,fractionated exposure to X-ray irradiation led to the significant depression of global DNA methylation level in blood (t =10.19 and 8.93,P ＜ 0.05).DNMT1 and MBD2 mRNA were down-regulated in PBMC,kidney and liver (t =5.06,3.01,3.97,12.25,3.50 and 3.73,P ＜0.05),and MBD2 was also down-regulated in spleen (t =3.03,P ＜ 0.05).However,no changes were observed in single exposed group.As for the delayed effects,the methylation levels of blood were not changed in the single or fractionated exposed groups,and only MBD2 mRNA was down-regulated in PBMC and brain of fractionated exposed group (t =3.52 and 2.85,P ＜ 0.05).Conclusions Fractionated LDR exposure can induce genome DNA hypomethylation,which is tissue-specific,and may be related with down-regulation of DNMT1 and MBD2.

Effects of long-term low-dose γ-rays exposure on radiosensitivity of human B lymphoblast cells / 中华放射医学与防护杂志

Objective To investigate the effects of long-term low-dose radiation (LDR) of γ-rays on the proliferation and radiosensitivity of human lymphoblast cells HMy2.CIR (HMy) and to elucidate the underlying mechanism.Methods HMy cells were divided into control group and long-term LDR group.For the long-term LDR treatment,HMy cells were fractionally exposed to a low dose of γ-rays,which could enhance cell proliferation,3 times per week for 4 weeks.After the long-term LDR exposure,part of the control and long-term LDR exposed cells were further irradiated with a challenging dose (2 Gy) of γ-rays.Then cell proliferation and radiosensitivity were assayed by CCK-8 kit,cell apoptosis,and γ-H2AX formation was measured by flow cytometry.Gene expressions of cyclinD1,PCNA,bcl-2 and bax were detected by RT-PCR.Results The long-term LDR significantly increased cell proliferation (t =9.607,P ＜ 0.01) accompanied with up-regulation of cell cycle regulation gene cyclinD1 (t =6.869,P ＜ 0.01),proliferation regulation gene PCNA (proliferating cell nuclear antigen) (t =9.229,P ＜ 0.01) and bcl-2 gene (t =2.662,P ＜ 0.05),but decreased the expression of pro-apoptotic gene bax (t =19.908,P ＜0.01) in HMy cells.Compared to untreated cells,the long-term LDR decreased cell radiosensitivity (t =8.896,P ＜ 0.01),including apoptosis induction (t =4.762,P ＜ 0.01) and γ-H2AX formation (t =10.264,P＜0.01).Conclusions The long-term LDR promoted cell proliferation by up-regulating cell cycle related genes,while it reduced the radiosensitivity of HMy cells with acquisition of apoptotic resistance.

The combined biological effects of low dose radiation, carbon monoxide, benzene and noise on rats / 中华放射医学与防护杂志

Objective To investigate the combined biological effects of low dose radiation,carbon monoxide,benzene and noise on rats.Methods Sixteen male SD rats were randomly divided into experiment group and control group.The experiment group was exposed to carbon monoxide,benzene,low dose radiation and noise daily,the control group was in common environment.Peripheral blood,organ index,and marrow DNA content were detected.Two-dimensional electrophoresis (2-DE) was performed on serum protein analysis.Differential expressed proteins were identified by a matrix assisted laser desorption/ionization time of flight mass spectrometry (MAIDI-TOF-MS).Results Compared to control group,the liver index,spleen index,thymus index,leukocytes,platelets count,and marrow DNA content of the experiment group were decreased significantly (t =2.732,4.141,3.053,2.211,2.668,11.592,P ＜0.05).12 altered proteins were detected and through identification,3 proteins were definite in terms of serum amyloid A-4 protein (SAA4),trichoplein keratin filament-binding protein (TCHP) and tubulin alpha-4A chain (TUBA4A).Conclusions The hematopoietic system and immune system of rats are damaged significantly with the changes of several serum protein expressions by the combined exposure of low dose radiation,carbon monoxide,benzene and noise.This study may provide new information for the mechanism of the combination effects.

Study on therapy of leukemia through proliferated NK cell induced by low-dose radiation in nude mice / 中华放射医学与防护杂志

Objective To separate NK cells of mice from NK cell separation medium and study inhibitory effect of proliferated NK cell induced by low dose radiation on the leukemia model of K562 cells.Methods Flow cytometry and 3H-TdR methods were respectively used to measure proliferation index and activity of NK cells treated with low-dose radiation( which means exposure dose in 20 cGy low LET beam or 5 cGy high LET beam).CD13 + cells were measured by flow cytometry and TNF-α content in blood-serum was detected by ELISA.In vivo,peripheral blood leucocyte count,index of liver,indexes of spleen and kidney were observed in control group and experimental group.Results The purity of NK cell separation was (82.54 ± 0.18)%.The proliferation index of NK cells at 24 hours after 80 mGy irradiated was 36.31 ± 1.32% ,(t =24.69,P ＜0.05).Killing activity of NK cell induced by low dose radiation to K562 cell was (12.59±0.63)%(t=6.63,P＜0.05)and the inhibition ratio was 29.52%.Conclusion The injection of proliferated NK cell induced by low dose radiation demonstrated significant inhibitory effect on the growth of leukemia nude mouse.