Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy.

Radiobiological modelling of the risk of radiation-induced tumours following high dose radiation implies a general form for the dose-response relationship. Generally, risk will rise with radiation dose at low doses, reach a maximum value and then decline with further increase in dose. The magnitude of risk and the dose at which this risk is maximum are strongly dependent on the kinetics of repopulation by surviving normal and mutant cells and on genetic factors likely to differ between tissues and between individuals. The most reliable way to reduce the risk of second tumours is to reduce radiation dose further at sites where the dose is already low. These sites are usually distant from the primary treatment volume. For illustrative purposes, we have compared the predicted relative risks of second tumours at "distant sites" for treatment plans giving similar dose distributions (dose volume histograms) at the primary site. We suggest that dose reduction to distant sites could be of significant benefit in reducing the risk of second tumours. Further improvement will require more detailed knowledge of the radiation sensitivities and mutagenicities, together with the repopulation kinetics of the various cell lineages within the treatment volume.     

Radiation doses in Sweden resulting from the Chernobyl fallout: a review

The risk associated with the Chernobyl fallout is the product of radiation dose and risk factor per dose unit. The radiation doses originate from inhalation of radioactive particles, ground irradiation from deposited nuclides and internal irradiation caused by contaminated food. In Sweden the largest dose contribution is due to external radiation. The deposition has been mapped by aerial measurements and in situ high-resolution gamma measurements at ground level over the whole country. On the basis of these measurements, population-weighted doses for external radiation have been estimated. Whole-body measurements on randomly selected individuals have been performed in order to estimate the average dose from internal irradiation. The collective dose, i.e. the sum of all individual doses, has been estimated to be about 1500 man-Sievert for the first year after Chernobyl and 5000-7000 man-Sievert for a 50-year period. Using a risk factor of 0.02 fatal cancers per man-Sievert the Chernobyl fallout over Sweden might cause 100-200 fatal cancers.     

低剂量率辐射生物效应的研究进展

辐射的剂量率能显著影响放射治疗的生物效应,降低剂量率就降低了生物效应。然而,当剂量率降低到一定阈值以下,DNA损伤不能激活细胞的探测器——共济失调毛细血管扩张症突变(ATM)基因以及ATM基因介导的损伤修复途径,因而出现细胞高的致死性,即"反剂量率效应"。在持续低剂量率照射下,主要有两条修复途径参与双链断裂(DSB)的修复,即非同源末端连接(NHEJ)修复和同源重组(HR)修复。这些修复系统在亚致死性损伤和产生剂量率效应中起重要作用,如果损伤得以完整和精确的修复,细胞的辐射敏感性就会发生改变;如果损伤不能被修复,则会诱导细胞凋亡。p53基因在低剂量率辐射引起的细胞周期阻滞和诱导细胞凋亡过程中起关键作用。     

Variation in radiation-induced apoptosis in ataxia telangiectasia lymphoblastoid cell lines

Purpose : To investigate and compare the ability of Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) from healthy individuals (normals) and ataxia telangiectasia (A-T) patients to undergo apoptosis after exposure to ionizing radiation. Materials and methods : Four normal and eight A-T LCL were exposed to doses of up to 20 Gy ionizing radiation. Apoptosis induction was studied 24 h after irradiation using three different methods: measurement of caspase-3 activity, PARP-1 cleavage and estimation of the sub-G 1 cell fraction. Results : Of the eight A-T LCL tested, all harbouring truncating ATM mutations, five had a higher level of spontaneous apoptosis than the normal LCL as assessed by the sub-G 1 cell fraction. Four of the eight A-T LCLs showed a similar level of radiation-induced apoptosis after exposure to 5 Gy as the normal LCL. The other four A-T LCL showed a greater radiation-induced apoptotic response, as assessed by at least one of the three techniques. Conclusions : LCL from A-T patients can undergo ionizing radiation-induced apoptosis in spite of a defect in ATM-p53-dependent signalling pathways. However, the apoptotic response is characterized by a large degree of variability between the A-T cell lines, the causes of which remain to be established.     

心血管病介入操作时患者受照剂量估算

放射诊疗新技术给人类带来了巨大的利益,放射性介入操作是其中最具代表性的一类新技术.然而在放射性介入操作的过程中,患者受照剂量在医用X射线诊断和治疗中是最高的,其剂量可能大到能引起皮肤和眼晶体辐射损伤,而且其防护也是目前职业辐射防护中最困难的.目前有60%左右的介入术是在心血管病的治疗中开展,心血管病介入操作时患者的辐射防护问题已引起了国内外广泛的重视,并开展了较为广泛的研究.大量的研究结果表明,心血管病放射性介入操作可能给患者造成值得重视的高剂量辐射.但是许多研究都是集中在表面剂量,这个量对评估患者的风险是远远不够的.在外照射情况下,当人体受穿透力强的辐射(X射线、γ射线、中子)照射一定剂量时,可造成深部组织和器官损伤,因此在研究表面剂量的同时,研究深部组织和器官的剂量也是至关重要的.由于放射性介入操作可能引起肿瘤和遗传这类随机性效应损伤,因此需要估算其有效剂量.     

DNA instability, paternal irradiation and leukaemia in children around Sellafield.

The chemical instability of DNA under physiological conditions requires that cells have highly developed processes for repairing stochastic single-strand damage. It is proposed here that provided ionizing-radiation-induced single-strand damage does not occur at a rate sufficient to perturb the dynamic steady state between degradation and repair, it can be regarded as "irrelevant' to biological effect, leaving double-strand damage and DNA-protein crosslinks as "relevant' damage to biological effect. At dose rates of approximately 0.05 Gy/min low-LET radiation the rate of induced single-strand damage equals that of the spontaneous damage, and in this region a transition, with increasing dose-rate, from constant effect to increasing effect, will be expected. This is observed in studies of specific locus mutation by radiation in the male mouse. The application of this biophysical principle governing the influence of radiation dose-rate, to the association observed between paternal preconceptional dose to Sellafield workers and childhood leukaemia in their offspring, shows that the likelihood of a causal relationship is extremely remote.     

Overview of radiation-induced skin cancer in humans

There are about a dozen studies of the incidence of skin cancer among irradiated populations with known skin doses that are available for estimating the risk of radiation-induced skin cancer. It is of note that they provide no evidence for a dose threshold and are compatible with a linear dose-response relationship, at least for ultraviolet radiation exposed skin. The studies also provide varying amounts of evidence concerning a number of other important issues in assessing skin cancer risk: types of skin cancer induced by ionizing radiation, the appropriateness of relative risk vs absolute risk models, combined effects of ionizing and UV radiations, and variations in sensitivity to skin cancer induction among demographic and genetic subgroups. Little epidemiological information is available on several factors, such as the RBE for high-LET radiation, the effects of dose protraction or fractionation, or variations in risk by age at irradiation. A reasonable estimate of skin cancer lethality was 0.2 per cent when weighted for the relative proportions of squamous cell and basal cell skin cancers. Average risk estimates of radiation-induced skin cancer incidence were: absolute risk (AR) of 8.5 X 10(-4) person-year-Sv and excess relative risk (RR) of 52 per cent/Sv. Lifetime skin cancer risk was calculated by life-table methods for males from exposures spread out over ages 20-60 years. The estimates for excess skin cancer incidence were 2 per cent and 11 per cent per Sv under the AR and RR models, respectively, while the corresponding mortality risks were 4 X 10(-5) and 2 X 10(-4) per Sv.     

Rationale for using multiple antioxidants in protecting humans against low doses of ionizing radiation

Health risks of low doses of ionizing radiation (10 cGy or less) may not be accurately estimated in humans by epidemiological study or mathematical modelling because of several inherent confounding factors including environmental, dietary and biological variables that cannot be accounted for in any radio-epidemiological study. In addition, the expression of radiation-induced damage in humans not only depends upon total dose, dose rate, linear energy transfer (LET), and fractionation and protraction of total doses, but also on repair mechanisms, bystander effects, and exposure to chemical carcinogens, tumour promoters and other toxins. It also depends upon the levels of anti-carcinogenic and anti-tumour promoting agents. Low doses of ionizing radiation should not be considered insignificant with regard to increasing the incidence of somatic mutations (neoplastic and non-neoplastic diseases) and heritable mutations in humans owing to its interaction with other toxins that can enhance damage produced by irradiation. It is very prudent to continue to support the well-established radiobiological concept that no radiation dose can be considered completely safe, and that all efforts must be made to reduce both the radiation dose and biological damage, no matter how small that damage might be, without sacrificing the benefits of radiation. Based on the results of many scientific experiments, formulations containing multiple antioxidants for biological protection against radiation damage in humans can be developed, and this strategy together with the existing physical concept of radiation protection, should further reduce potential risks of low doses of ionizing radiation in humans.     

Radiation dose and risk of patients through nuclear medical procedures in the GDR. A comparison of 1978 and 1981

For the years 1978 and 1981 we compared the radiation dose for the patients examined by in vivo methods after administration of radiopharmaceuticals (27 procedures). The somatic effective dose equivalent, the effective collective dose, the somatic radiation risk, and the number of induced malignancies were calculated according to ICRP publication No. 26. All the procedures give rise to a radiation-induced somatic risk from the 4th up the 7th order. In recent years we have seen an increase of the application of 99mTc compounds and a decrease in the use of 131I-sodium iodide. A comparison of the results for the two years shows the expected reduction of radiation dose and risk.     

Variation in radiation-induced apoptosis in ataxia telangiectasia lymphoblastoid cell lines

PURPOSE: To investigate and compare the ability of Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) from healthy individuals (normals) and ataxia telangiectasia (A-T) patients to undergo apoptosis after exposure to ionizing radiation. MATERIALS AND METHODS: Four normal and eight A-T LCL were exposed to doses of up to 20 Gy ionizing radiation. Apoptosis induction was studied 24 h after irradiation using three different methods: measurement of caspase-3 activity, PARP-1 cleavage and estimation of the sub-G(1) cell fraction. RESULTS: Of the eight A-T LCL tested, all harbouring truncating ATM mutations, five had a higher level of spontaneous apoptosis than the normal LCL as assessed by the sub-G(1) cell fraction. Four of the eight A-T LCLs showed a similar level of radiation-induced apoptosis after exposure to 5 Gy as the normal LCL. The other four A-T LCL showed a greater radiation-induced apoptotic response, as assessed by at least one of the three techniques. CONCLUSIONS: LCL from A-T patients can undergo ionizing radiation-induced apoptosis in spite of a defect in ATM-p53-dependent signalling pathways. However, the apoptotic response is characterized by a large degree of variability between the A-T cell lines, the causes of which remain to be established.     

Overview of Radiation-induced Skin Cancer in Humans

Summary

There are about a dozen studies of the incidence of skin cancer among irradiated populations with known skin doses that are available for estimating the risk of radiation-induced skin cancer. It is of note that they provide no evidence for a dose threshold and are compatible with a linear dose–response relationship, at least for ultraviolet radiation exposed skin. The studies also provide varying amounts of evidence concerning a number of other important issues in assessing skin cancer risk: types of skin cancer induced by ionizing radiation, the appropriateness of relative risk vs absolute risk models, combined effects of ionizing and UV radiations, and variations in sensitivity to skin cancer induction among demographic and genetic subgroups. Little epidemiological information is available on several factors, such as the RBE for high-LET radiation, the effects of dose protraction or fractionation, or variations in risk by age at irradiation. A reasonable estimate of skin cancer lethality was 0·2 per cent when weighted for the relative proportions of squamous cell and basal cell skin cancers. Average risk estimates of radiation-induced skin cancer incidence were: absolute risk (AR) of 8·5 × 10^?4 person-year-Sv and excess relative risk (RR) of 52 per cent/Sv. Lifetime skin cancer risk was calculated by life-table methods for males from exposures spread out over ages 20–60 years. The estimates for excess skin cancer incidence were 2 per cent and 11 per cent per Sv under the AR and RR models, respectively, while the corresponding mortality risks were 4 × 10^?5 and 2 × 10^?4 per Sv.     

A hypothesis: radiation carcinogenesis may result from tissue injuries and subsequent recovery processes which can act as tumor promoters and lead to an earlier onset of cancer

Cancer risks from radiation can be observed as an increase in mortality when compared to a control group. However, it is unknown if this increased risk results from the induction of cancer or from an earlier onset of cancer. In mouse studies, it has been repeatedly shown that after an irradiation, the survival curve is shifted toward lower ages, but remains parallel to the control curve, and the extent of the shift in time to lower ages is dose-dependent. This shift is not satisfactorily explained by the induction model which assumes that cancers in the exposed group consist of spontaneous and induced events. Consequently, it seems that this shift could be interpreted to mean that all animals in the exposed group had suffered from life shortening. Under this scenario, however, it turns out that the radiation effects can no longer be interpreted as the result of oncogenic mutations, because these effects would have to involve all tumors, and the effectiveness of radiation changes with the dose. This leads to the speculation that radiation exposures induce a broad range of tissue injuries, and that these injuries are subsequently subjected to longlasting systemic recovery processes which act as promoters for tumor cells. In other words, potential cancer stem cells which were located in the irradiated field can escape oncogenic damage but undergo stimulation later in life toward the development of malignancy from radiation-induced activated microenvironment. This is an unusual form of the non-targeted or bystander effects of radiation. It is worth noting that this model suggests that there could be a path or paths which could be used to intervene in the process of post-exposure carcinogenesis, and that cancer risks at low doses could be described as days or weeks of life lost.     

Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice

Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation.

Materials and methods: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0.1) or intermediate/high (0.2–1?Gy) doses of radiation either by acute X-rays exposure or protracted exposure to low dose-rate γ-radiation was used to analyse by PCR the presence of illegitimate TR gene rearrangements.

Results: Radiation exposure does not increase the onset of TR gene trans-rearrangements in irradiated mice. In mice where it happens, trans-rearrangements remain sporadic events in developing T lymphocytes.

Conclusion: We concluded that low dose/low dose rate ionizing radiation (IR) exposure does not lead to widespread inactivation of ATM-dependent mechanisms, and therefore that the mechanisms enforcing genetic stability are not impaired by IR in developing lymphocytes and lymphocyte progenitors, including BM-derived hematopoietic stem cells, in low dose/low dose rate exposed mice.     

Potential hazards of diagnostic radiation.

There are no precise data for determining the extent of somatic damage from small doses of radiation used in diagnostic radiology. Diagnostic radiation given to pregnant women, knowingly or unknowingly, should rarely reach teratogenic levels causing brain and eye abnormalities. Evidence suggests that it does increase the risk of childhood malignancy, especially leukemia. Although rapidly growing tissues seem most susceptible, all radiation probably carries a very small risk of carcinogenesis. Genetic damage is equally difficult to estimate. Diagnostic radiation of females, even in childhood, may be related to an increased incidence of Down's syndrome in older mothers. Radiation also causes point mutations, which may explain the increase of some genetic abnormalities in progeny of older fathers. Whenever an abdominal or pelvic radiograph is ordered before the end of the reproductive period, there must be a potential benefit to balance the small risk involved.     

Induction of unstable and stable chromosomal aberrations by 99mTc: in-vitro and in-vivo studies

BACKGROUND: Biological dosimetry, which determines the dose of acquired radiation by measuring radiation-induced variation of biological parameters, can help assess radiation damage in an individual. Evaluation of radiation exposure requires setting up reference curves for each type of radiation. AIM: To evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. METHODS: Dicentrics, rings, excess fragments, complete reciprocal translocations and incomplete reciprocal translocations were scored in peripheral blood lymphocytes from patients exposed to a 99mTc bone scintigraphy. A specific relationship between the radiation dose delivered by 99mTc and the frequency of stable and unstable chromosomal aberrations was established in vitro to estimate whole-body dose. Chromosome analysis using fluorescence plus Giemsa and fluorescence in-situ hybridization was undertaken on six patients before and after a 99mTc bone scintigraphy. Dicentrics, rings, excess fragments, and translocations were scored in blood lymphocytes after in vitro 99mTc external irradiation in order to construct dose calibration curves. RESULTS: Analysis of the in-vitro data shows that the number of both unstable and stable aberrations has a quadratic linear relationship to the dose. Our in-vivo irradiation studies showed that activities of 99mTc-hexamethylene diphosphonate (99mTc-HDP) used for bone investigations do not induce any additional unstable chromosome aberrations and translocations. The frequencies obtained did not differ significantly from background values. CONCLUSIONS: 99mTc can produce unstable and stable chromosomal aberrations in vitro. 99mTc-HDP administration does not induce supplementary chromosomal aberrations. The dose-response curves will allow a more accurate evaluation of the risk related to in-vivo administration of 99mTc labelled radiopharmaceuticals, and they can be used to assess the safe upper limit of injected activity in humans.     

香烟和绿茶对辐射致突变效应的影响

目的 探讨日常生活中的香烟和绿茶因素对辐射致突变效应的影响,为放射损伤的防护提供基础资料。方法 按照析因实验设计,香烟、绿茶和辐射3因素用与不用2个水平（23）分为8个实验组。动物分组采用分层随机化。各组分别给予香烟、绿茶和辐射,以及3因素的各种不同组合,其中1组为空白对照组。单盲法测定小鼠骨髓嗜多染红细胞微核率。实验数据用SAS 8.0分析软件进行析因实验设计的方差分析。结果 对于诱发骨髓细胞突变的效应,辐射因素、香烟因素、绿茶因素,其中香烟与辐射的交互作用差异有统计学意义（P＜0.01）,绿茶与辐射的交互作用差异有统计学意义（P＜0.05）。结论 辐射和吸烟均具有致突变作用,绿茶具有抑制细胞突变的作用,吸烟与辐射有协同致突变作用,绿茶对辐射的致突变性有拮抗作用。     

Damage to the heart from tumor irradiation in the thorax--an echocardiographic study

The authors give a review of 74 patients with radiation-induced heart disease which could be easily detected by echocardiography. In almost all of the patients a pericardial effusion (P.E.), with relative sinus tachycardia was found 3 to 4 weeks after onset of radiation and this was transient in some cases. This phenomenon was interpreted as an early radiation-induced reaction of the heart. 6 to 12 months after radiation, late damage of the heart occurred depending on field and total radiation dose. This manifested as massive P.E. with changes in ECG. Later there was damage to the myocardium caused by coronary sclerosis. The tendency to constrictive pericarditis was manifested not earlier than 3 years or later after radiation. The authors advise follow up of the irradiated patients case by case, checked by echocardiography, especially those who received more than 5000 rad to the heart area and therefore have high risk of late heart damage.     

Radiation dose and risk of patients through nuclear medical procedures in the GDR

For the years 1978 and 1981 we compared the radiation dose for the patients examined by in vivo methods after administration of radiopharmaceuticals (27 procedures). The somatic effective dose equivalent, the effective collective dose, the somatic radiation risk, and the number of induced malignancies were calculated according to ICRP publication No. 26.All the procedures give rise to a radiation-induced somatic risk from the 4th up the 7th order. In recent years we have seen an increase of the application of ^99mTc compounds and a decrease in the use of ¹³¹I-sodium iodide. A comparison of the results for the two years shows the expected reduction of radiation dose and risk.Dedicated to Ernst W. Doerffel, Honorary President of the GDR-Society of Nuclear Medicine, on occasion of his 75th anniversary     

玻璃电子自旋共振剂量学特性的研究进展

辐照后的玻璃可经电子自旋共振（ESR）波谱仪检测出ESR信号,包括本底信号、机械信号和辐射信号。ESR信号的大小与受照剂量基本成正比。当发生核事故或突发辐射意外时,可以通过对受照人员随身携带物品或事故区域内的玻璃进行ESR测量,快速估算事故剂量,评价事故的严重程度,并对受照人员进行及时的医学救治。玻璃具有廉价、化学惰性、刚度好、易于处理、普遍易得等特点,是一种很有前景的剂量估算物理剂量计。笔者主要对玻璃构成、剂量估算原理、ESR信号组成及其剂量学特性进行了探讨。