A cluster of childhood leukaemias near two neighbouring nuclear installations in Northern Germany: prevalence of chromosomal aberrations in peripheral blood lymphocytes

PURPOSE: Between 1990 and 1991 a leukaemia cluster was observed in children living close to the combined site of a nuclear power plant and a nuclear research facility in Elbmarsch, a region in Lower Saxony (Germany). We aim to investigate the prevalence of presumably radiation-induced chromosomal aberrations in peripheral blood lymphocytes of children in Elbmarsch and children of a control region in order to find out whether there was an uncontrolled release of radioactive material which resulted in a substantial exposure. MATERIALS AND METHODS: The frequency of dicentric and ring chromosomes in lymphocytes of the peripheral blood in 42 children in Elbmarsch and 30 children in Pl?n was investigated. Children in both groups had been permanent residents of the study area. RESULTS: The mean frequency of dicentric and ring chromosomes in Elbmarsch was 14/32580 cells (=0.430 x 10(-3); 95% CI 0.24-0.70 x 10(-3) cells), and in Pl?n it was 17/24065 cells (=0.706 x 10(-3); 95% CI 0.42-1.10 x 10(-3) cells). CONCLUSIONS: No difference in the frequency of dicentric and ring chromosomes was observed between children in Elbmarsch living close to a combined site of a nuclear power plant and a nuclear research facility and children living in the control area Pl?n. The power of the study to detect a threefold or higher increase in the aberration frequency was at least 0.86.     

甘肃某矿区周围居民恶性肿瘤死亡调查

目的 评价核设施在正常运行50年后对周围人群的健康影响.方法 调查甘肃某矿区周围30 km范围内居民2004-2008年人口资料、全部实体癌和白血病的死亡率.结果 调查地区居民2004-2008年全癌死亡率和标化死亡率分别为95.51/105和93.56/105,白血病死亡率和标化死亡率分别为2.44/105和2.22/105.对照区2004--2008年间恶性肿瘤死亡率和标化死亡率分别为106.88/105和89.31/105,白血病仅死亡1例,死亡率为3.56/105.结论 甘肃某矿区运行50年后,周围居民的恶性肿瘤和白血病死亡率未见增加,该矿区的生产和运行未对周围居民健康造成不良影响.

Abstract：

Objective To evaluate the cancer risk among the inhabitants around a certain nuclear facility of Gansu Province after operation for nearly 50 years.Methods Specially developed forms were filled by countryside doctors in the villages 30 km on the leeward or at the lower reaches of Yumen City,Gansu Province where a nuclear facility had operated for nearly 50 years,to register the relevant data of those who died of solid cancer and leukemia during the period from 1 January 2004 to 31 December 2008 based on the relevant data and household survey.A town 90 km away from the nuclear facility with 4181 people were regarded as control area.Results The crude mortality and standardized mortality rate(SMR) of cancer were 95.51×10-5 and 93.56×10-5.respectively.The crude mortality and SMR of leukemia were 2.44×10-05 and 2.22×10-05, respectively.and the crude mortality and SMR of cancer were 106.88×10-05, and 89.31×10-5, respectively.The crude mortality and SMR of leukemia were 2.44×10-05 and 2.22×10-5, respectively in the investigated area,and the crude mortality of leukemia was 3.56×10-5 (only one leukemia cage died)in the control area in the same time.The cancer and leukemia mortality rates of the investigated area were similar to those of control area.Conclusions Nuclear facility does not significantly increase the cancer mortality among the residents living nearby.     

Automated scoring of dicentric chromosomes differentiates increased radiation sensitivity of young children after low dose CT exposure in vitro

Purpose: Automated detection of dicentric chromosomes from a large number of cells was applied to study age-dependent radiosensitivity after in vitro CT exposure of blood from healthy donors.

Materials and methods: Blood samples from newborns, children (2–5 years) and adults (20–50 years) were exposed in vitro to 0 mGy, 41 mGy and 978 mGy using a CT equipment. In this study, automated scoring based on 13,000–31,000 cells/dose point/age group was performed. Results for control and low dose points were validated by manually counting about 26,000 cells/dose point/age group.

Results: For all age groups, the high number of analyzed cells enabled the detection of a significant increase in the frequency of radiation induced dicentric chromosomes in cells exposed to 41 mGy as compared to control cells. Moreover, differences between the age groups could be resolved for the low dose: young donors showed significantly increased risk for induced dicentrics at 41 mGy compared to adults.

Conclusions: The results very clearly demonstrate that the automated dicentric scoring method is capable of discerning radiation induced biomarkers in the low dose range (<100 mGy) and thus may open possibilities for large-scale molecular epidemiology studies in radiation protection.     

M-FISH技术检测辐射诱导染色体易位和双着丝粒畸变

目的　探讨用多色荧光原位杂交 (M FISH)技术检测的易位和双着丝粒染色体畸变的差异。方法　用 1,2 ,3,7,8,9,14和 15号染色体端粒和着丝粒特异性探针的M FISH方法 ,分析6 0 Coγ射线离体照射的脐带血淋巴细胞染色体易位和双着丝粒畸变。结果　 (1)用M FISH方法分析6 0 Coγ射线诱导的易位和双着丝粒染色体畸变的剂量 效应曲线 ,均符合线性二次剂量效应模式 ;易位与双着丝粒的比值在大多数剂量水平不等于 1。 (2 )细胞中无非稳定性畸变的完全相互易位的比例随着吸收剂量的增加而降低。 (3)对大多数被标记染色体 ,3 0 0Gyγ射线照射诱发的染色体畸变观察值与理论值无差别 ;9号染色体畸变 (易位和双着丝粒 )观察值显著高于理论值 (P <0 0 5或P <0 0 1) ,15号染色体易位观察值显著低于理论值 (P <0 0 1)。结论　电离辐射诱导的染色体易位率不等于双着丝粒畸变率 ;对于大多数染色体 ,辐射诱发染色体易位率和双着丝粒畸变率符合随机性规律。     

Characteristics of the solid state nuclear detector CR-39 for neutron radiography purposes

The solid state nuclear track detector CR-39, together with a natural boron converter screen have been used as an image-detector system for neutron radiography purposes. In order to determine its radiographic characteristics, the image-detector system was irradiated up to neutron exposures around 6×10¹⁰ n/cm² in a radiography facility installed at the IEA-R1 Nuclear Research Reactor. The detectors were chemically etched in a KOH (30%) aqueous solution at 70°C. The best radiography conditions were obtained for neutron exposures ranging from 1×10⁹ to 2×10¹⁰ n/cm² and for 25 min etching time. The present results were compared with those determined for other track detectors and discussed according to the theory of the image formation in solid state nuclear track detectors. This theory is based on the optical properties of a single track.     

高本底辐射诱发居民外周血淋巴细胞染色体畸变的剂量效应关系

目的通过人群调查探讨高本底辐射诱发居民染色体畸变的剂量效应关系,为建立环境小剂量辐射剂量效应模型和评估群体剂量提供参考。方法３９名调查对象选自高本底和对照地区１３个家庭中的祖、父、子三代成员。个体累积剂量分别为２３９～２６１３和５２～２９８ｍＧｙ。分离淋巴细胞培养法制备染色体标本,总计观察细胞数约１０００００。结果①在高本底组每一家庭中均观察到个体染色体畸变率随年龄增加而升高,其趋势在户间差异无显著性。②高本底组不同年龄个体染色体畸变率与年龄和累积剂量密切相关,可拟合为线性一次式：Ｙａｇｅ＝００４４８Ｘ＋０４９１３（Ｒ２＝０７８１４）;Ｙｄｏｓｅ＝００１５６Ｘ＋０５７１５（Ｒ２＝０７０６１）;③对照组个体间畸变率差异不显著,其平均畸变率接近正常人群自发畸变率。结论高本底持续照射诱发的人体内双着丝点加环畸变随受照时间的延长而持续升高。双加环畸变分析可作为小剂量持续照射的可信赖的生物剂量仪,但存在一个应用上的累积剂量阈值,其值约为５０ｍＧｙ。     

Chromosomal alterations in peripheral lymphocytes of female cabin attendants.

PURPOSE: To analyse lymphocyte chromosomes from female cabin attendants flying the North Atlantic route. MATERIALS AND METHODS: Peripheral lymphocytes from 58 cabin attendants and 29 controls, all female, were cultured and analyzed for structural chromosomal aberrations and sister chromatid exchanges (SCE). Cytogenetic data from 56 age-matched females from Berlin investigated between 1994 and 1996 as part of routine medical checks were used as an additional control group. RESULTS: The mean frequencies of dicentric and ring chromosomes per 1000 cells amount to 1.3+/-0.2 in cabin attendants, 1.4+/-0.2 in ground personnel and 1.3+/-0.2 in the Berlin control group. Sister chromatid exchanges were found at mean frequencies of 7.0+/-0.1, 6.8+/-0.1 and 6.8+/-0.2 per cell respectively in the three groups. CONCLUSIONS: When compared with controls, cabin attendants have no elevation of the frequencies of dicentric and ring chromosomes and SCE.     

Chromosomal alterations in peripheral lymphocytes of female cabin attendants

Purpose: To analyse lymphocyte chromosomes from female cabin attendants flying the North Atlantic route. Materials and methods: Peripheral lymphocytes from 58 cabin attendants and 29 controls, all female, were cultured and analyzed for structural chromosomal aberrations and sister chromatid exchanges (SCE). Cytogenetic data from 56 age-matched females from Berlin investigated between 1994 and 1996 as part of routine medical checks were used as an additional control group. Results: The mean frequencies of dicentric and ring chromosomes per 1000 cells amount to 1.3 +/- 0.2 in cabin attendants, 1.4 +/- 0.2 in ground personnel and 1.3 +/- 0.2 in the Berlin control group. Sister chromatid exchanges were found at mean frequencies of 7.0 +/- 0.1, 6.8 +/- 0.1 and 6.8 +/- 0.2 per cell respectively in the three groups. Conclusions: When compared with controls, cabin attendants have no elevation of the frequencies of dicentric and ring chromosomes and SCE.     

基于人工智能的双着丝粒染色体识别算法初步研究

目的:为解决双着丝粒染色体人工分析费时费力的问题,探索人工智能技术,提出一种实现双着丝粒染色体自动识别的算法,从而实现快速高通量生物剂量估算。方法:结合人工智能和图像处理技术,基于MATLAB软件,通过研究图像预处理、阈值分割、二值化处理、区域标识、卷积神经网络和双着丝点识别算法,定义模糊隶属度函数来描述每条染色体属于...     

Book Announcement

In parallel to delayed reproductive death and delayed micronuclei in surviving V79 cells that have been reported, the frequency of apoptosis and dicentrics was investigated in the same cell line, 1-2 weeks after X-ray doses between 1 and 12Gy. Apoptosis was assessed by morphological criteria after staining with Giemsa and using the ApoptagTM method in parallel. The frequency of apoptosis peaked 48 h after irradiation at about 35% as a function of dose and then decreased to about 10% on day 3. It remained 10 times higher than in unirradiated cells until day 14. The frequency of dicentric chromosomes 24h after irradiation increased according to a linear-quadratic function, up to about 110% after 12 Gy, decreased 3 days later to about 10% and remained about 5-fold higher than in control cells. The dose-response relationship was similar for all the various end-points of expression of radiation induced genomic instability, showing a steep increase of the frequency with dose up to 3-4Gy and with no further increase at higher radiation doses.     

儿童脉管性疾病患者介入手术后外周血淋巴细胞染色体畸变观察

目的:评估儿童脉管性疾病患者在介入手术过程中接受的电离辐射(IR)对患儿染色体畸变的影响。方法:在知情同意的条件下,于介入术前和术后立刻采集26名患儿的外周血1.2 ml,培养制备染色体,分析外周血淋巴细胞染色体畸变情况。结果:儿童介入术后双着丝粒染色体+着丝粒环(dic+r)率明显增加,与术前比较,差异有统计学意义(...     

Sister chromatid exchanges in ring chromosomes following X-irradiation of human lymphocytes

PURPOSE: To examine whether X-rays induce sister chromatid exchanges (SCE). MATERIALS AND METHODS: Peripheral lymphocytes irradiated in vitro or in vivo were cultured and treated with okadaic acid to generate premature chromosome condensation (PCC). When identical spreads were analysed using conventional Giemsa staining and pan-centromeric fluorescence in situ hybridization painting, ring chromosomes were observed. RESULTS: In PCC preparations, cells in the late G(2) phase and late M phase were observed. In late M phase cells, 17-20% of ring chromosomes lacked one chromatid (single-chromatid ring), irrespective of dose. Both the distribution patterns of centromeres in rings and intercentromere distances in dicentric rings indicate that a considerable number of single-chromatid rings might be formed by SCE occurring in a chromosome-type ring, thereby joining strands of two rings, followed by a transformation into one ring. These single-chromatid rings were less stable in vivo than chromosome-type rings. CONCLUSION: Single-chromatid rings visualized clearly using PCC techniques indicate SCE in the respective rings. Contrary to the conventional SCE-detecting technique, this approach does not require the use of bromodeoxyuridine, which itself leads to SCE. Some of the observed SCE might be secondary products resulting from the repair of radiation-induced DNA damage, while others may be spontaneous.     

Chromosome Aberrations Induced in Human Lymphocytes by Ultrasoft AlK and CK X-rays

Summary

Induction of structural chromosome aberrations was studied in human peripheral blood lymphocytes irradiated in the unstimulated state with ultrasoft X-rays. Aluminium K X-rays (1·49 keV) and carbon K X-rays (0·28 keV) were used. The frequencies of dicentric aberrations and of excess acentric fragments were found to increase approximately linearly with absorbed dose of both radiations. Carbon X-rays were more effective than aluminium X-rays. The corresponding linear yield coefficients for dicentrics are (3·7 × 10^?1) Gy^?1 and (2·2 × 10^?1) Gy^?1 respectively. At low doses both these radiations are more effective than hard X-rays in producing dicentric aberrations, but at high doses aluminium X-rays are less effective than hard X-rays because of the large positive curvature of the hard X-ray dose-response. The most significant observation of these experiments is that electrons of less than 280 eV, produced by carbon X-rays, are efficient in producing dicentric aberrations. This implies that single local energy events of about 14 ionizations within less than 7 nm are able to produce exchange aberrations.     

Chromosome aberrations in peripheral lymphocytes of patients irradiated with 15-MeV-photons for Morbus Hodgkin

Chromosome aberrations in peripheral lymphocytes of two Morbus Hodgkin patients were analyzed before and during the ongoing radiotherapy. Venous blood was taken 5 min after and before a successive irradiation in order to examine the dose dependence as well as the influence of mixed unirradiated and irradiated lymphocytes on the aberration rate. Both patients showed an overdispersed distribution of dicentric chromosomes and acentric fragment from the outset of therapy and independent of the time blood was taken. The dose-effect relationship established for both types of aberrations by the Maximum-Likelihood approach may best be described as being linear. The dose effect curves 5 min after a fraction did not differ from those calculated for a time thereafter. However, after the first two irradiations, the rate of dicentric chromosomes in the blood samples taken at a later time was about twice as high as that in the samples taken 5 min after irradiation. Dicentric chromosomes were twice more frequent during the entire radiotherapy than acentric fragments and about 30 times more frequent than centric ring chromosomes.     

核电站周边地表水中铀的同位素丰度分析

目的 掌握核电站周边地区地表水中铀同位素丰度比值基线数据.方法 采集江苏、山东、浙江省境内3个核电站周边地区供饮用的地表水,利用磷酸三丁酯(TBP)萃淋树脂分离富集铀,电感耦合等离子体质谱(ICP-MS)法分析样品中的234 U/238U与235 U/238U的丰度比.结果 地表水中234 U/238U丰度比范围为4.575×10-5 ～7.752×10-5,235 U/238U丰度比范围为7.273 ×10-3～7.639×10-3.结论 地表水中234U被不同程度地富集.     

Bowman–Birk protease inhibitor activates DNA‐dependent protein kinase and reduces formation of radiation‐induced dicentric chromosomes

Purpose: To test a stimulatory effect of the radioprotector Bowman Birk protease inhibitor (BBI) upon DNA repair processes.

Materials and methods: An effect of BBI upon DNA repair was investigated by quantification of radiation‐induced dicentric chromosomes. Sensitivity to ionizing radiation was determined by clonogenic survival assay. Quantification of activity of the DNA‐dependent kinase was performed by immunoprecipitation and phosphorylation of a TP53‐derived peptide.

Results: The formation of radiation‐induced dicentric chromosomes was reduced significantly after pretreatment of cells with BBI. By using a cell line with an inducible expression of a mutated TP53, it was shown that the BBI‐mediated reduction of dicentric chromosome formation depended on the presence of wild‐type TP53. To get further insights into the molecular mode of action of BBI, activity of the DNA‐dependent protein kinase (DNA‐PK) was quantified. BBI treatment resulted in a stimulation of basal (DNA‐PK) activity. In SCID mouse fibroblasts deficient in DNA‐PK activity, BBI failed to reduce the amount of radiation‐induced dicentric chromosomes and the radioprotective effect was absent. Likewise, cells expressing mt.TP53 did not show radioprotection by BBI.

Conclusions: It was observed that BBI exerts its radioprotective effect by a reduction of incorrect DNA repair, resulting in a reduced amount of dicentric chromosomes. This effect on the fidelity of DNA repair is TP53 dependent and correlated with induction of DNA‐PK activity.     

Bowman-Birk protease inhibitor activates DNA-dependent protein kinase and reduces formation of radiation-induced dicentric chromosomes

PURPOSE: To test a stimulatory effect of the radioprotector Bowman Birk protease inhibitor (BBI) upon DNA repair processes. MATERIALS AND METHODS: An effect of BBI upon DNA repair was investigated by quantification of radiation-induced dicentric chromosomes. Sensitivity to ionizing radiation was determined by clonogenic survival assay. Quantification of activity of the DNA-dependent kinase was performed by immunoprecipitation and phosphorylation of a TP53-derived peptide. RESULTS: The formation of radiation-induced dicentric chromosomes was reduced significantly after pretreatment of cells with BBI. By using a cell line with an inducible expression of a mutated TP53, it was shown that the BBI-mediated reduction of dicentric chromosome formation depended on the presence of wild-type TP53. To get further insights into the molecular mode of action of BBI, activity of the DNA-dependent protein kinase (DNA-PK) was quantified. BBI treatment resulted in a stimulation of basal (DNA-PK) activity. In SCID mouse fibroblasts deficient in DNA-PK activity, BBI failed to reduce the amount of radiation-induced dicentric chromosomes and the radioprotective effect was absent. Likewise, cells expressing mt.TP53 did not show radioprotection by BBI. CONCLUSIONS: It was observed that BBI exerts its radioprotective effect by a reduction of incorrect DNA repair, resulting in a reduced amount of dicentric chromosomes. This effect on the fidelity of DNA repair is TP53 dependent and correlated with induction of DNA-PK activity.     

《中华放射医学与防护杂志》创办者之一姚家祥(1922—2021)

《中华放射医学与防护杂志》的创办者之一、中国疾控中心辐射安全所姚家祥研究员因病医治无效,于2021年12月23日上午7点40分逝世,享年100岁。     

双着丝粒染色体自动分析研究进展

双着丝粒染色体分析作为生物剂量估算的“金标准”,在大规模核辐射事件中对于快速做出临床决策至关重要。传统人工分析费时费力,通量低,且对人员的技术要求高,难以满足大规模核事故情况下大量人员剂量估算的要求。近年来,针对大规模辐射事件下受照人员高通量、快速、准确的剂量估算需求,研究者们开发了多种策略。本文介绍了双着丝粒染色体自动分析检测方法的研究进展,为国内同行开展基于双着丝粒染色体指标估算生物剂量研究提供参考。     

Chromosome aberrations in patients irradiated for pelvic tumours

Peripheral blood lymphocytes of patients undergoing radiation therapy for pelvic tumours have been examined for the presence of dicentric and centric ring chromosomes. Blood samples were taken, by venipuncture, prior to the first radiotherapy session and 24 h after radiotherapy sessions to allow the mixing of the irradiated lymphocytes in the circulating blood. The yield of dicentrics and centric rings was best fitted by a straight line which, according the maximum likelihood method, corresponds to Y = 1.77 +/- 0.0003 10(-2) D. On this basis the dose inducing ten dicentrics or rings is 5.62 Gy at the target volume and, thus, is intermediate between the doses at the target volumes displaying the same effects in patients treated for mammary carcinoma (15 Gy) or for ankylosing spondylitis (2 Gy).