Hyperfast,early cell response to ionizing radiation

Purpose : To determine whether the oscillatory changes of radiosensitivity which occur within fractions of a second to a few minutes following flash irradiation correlate with an altered incidence of apoptosis, DNA strand breaks or lipid-coupled signalling. Materials and methods : Human tumor cells (SQ-20B, LoVo) or Chinese hamster V79 fibroblasts were exposed to split-dose, pulse irradiation with 3.5 MeV electrons at high dose-rate (12 or 120Gys -1) and the effects assessed by clonogenic assays, analysis of DNA cleavage and microscopic observation. Results : The processes underlying oscillatory radiation response were saturable, but did not correlate with an increased incidence of DNA single- or double-strand breaks or apoptosis. N -acetylcysteine and inhibitors of lipid-derived signalling also failed to alter oscillatory response. However, this response did correlate with phenotypic alterations evoking mitotic or delayed cell death. Furthermore, high dose-rate irradiation provided a lower level of instability than protracted γ-ray irradiation. Conclusions : It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchronous remodeling of chromatin, evoking enhanced chromosome damage upon re-irradiation.     

Hyperfast, early cell response to ionizing radiation

PURPOSE: To determine whether the oscillatory changes of radio-sensitivity which occur within fractions of a second to a few minutes following flash irradiation correlate with an altered incidence of apoptosis, DNA strand breaks or lipid-coupled signalling. MATERIALS AND METHODS: Human tumor cells (SQ-20B, LoVo) or Chinese hamster V79 fibroblasts were exposed to split-dose, pulse irradiation with 3.5 MeV electrons at high dose-rate (12 or 120 Gy x s(-1)) and the effects assessed by clonogenic assays, analysis of DNA cleavage and microscopic observation. RESULTS: The processes underlying oscillatory radiation response were saturable, but did not correlate with an increased incidence of DNA single- or double-strand breaks or apoptosis. N-acetylcysteine and inhibitors of lipid-derived signalling also failed to alter oscillatory response. However, this response did correlate with phenotypic alterations evoking mitotic or delayed cell death. Furthermore, high dose-rate irradiation provided a lower level of instability than protracted gamma-ray irradiation. CONCLUSIONS: It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchronous remodeling of chromatin, evoking enhanced chromosome damage upon re-irradiation.     

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.     

Brain Atrophy after Foetal Exposure to Very Low Doses of Ionizing Radiation

Acute, high dose-rate, exposure of the rat embryo on day 15 post-conception (PC) causes a reduction of brain weight in adult life that is proportional to the dose received. Doses as low as 10 mGy of 600 keV neutrons, from a Van de Graaff accelerator, or 100 mGy of 250 kV X-rays are capable of eliciting a significant effect. The relative biological effectiveness for acute neutron exposure compared with 250 kV X-rays was 3·5. A brain weight reduction was also observed after gammaray exposures protracted over 4 or 6 days, during cerebral corticogenesis. The dose-rate reduction factor was only 1·5 for exposure from days 12 to 16 PC and 3·3 for exposure from days 14 to 20 PC. In relation with the decrease in brain weight, the cingulum bundle, a myelinated structure associated with the corpus callosum, displayed a significant reduction in size. The implications of these observations for human exposures are discussed.     

Brain atrophy after foetal exposure to very low doses of ionizing radiation.

Acute, high dose-rate, exposure of the rat embryo on day 15 post-conception (PC) causes a reduction of brain weight in adult life that is proportional to the dose received. Doses as low as 10 mGy of 600 keV neutrons, from a Van de Graaff accelerator, or 100 mGy of 250 kV X-rays are capable of eliciting a significant effect. The relative biological effectiveness for acute neutron exposure compared with 250 kV X-rays was 3.5. A brain weight reduction was also observed after gamma-ray exposures protracted over 4 or 6 days, during cerebral corticogenesis. The dose-rate reduction factor was only 1.5 for exposure from days 12 to 16 PC and 3.3 for exposure from days 14 to 20 PC. In relation with the decrease in brain weight, the cingulum bundle, a myelinated structure associated with the corpus callosum, displayed a significant reduction in size. The implications of these observations for human exposures are discussed.     

Oxidative and nitrative stress-related changes in human lens epithelial cells following exposure to X-rays

Purpose: There is limited understanding of the mechanistic effects of ionizing radiation (IR) exposure in cataract formation. In this study, we explored the effects of IR on reactive oxygen/nitrogen species (ROS and RNS) generation in human lens epithelial (HLE) cells as an early key event to long-term damage.

Materials and methods: HLE cell-line was exposed to X-rays at varied doses (0–5?Gy) and dose-rates. Cell lysates and supernatants were collected 20?h post-exposure and analysed for viability, cell cycling and metabolites of ROS (p, m-, o-, tyrosines, 3-chlorotyrosine (cl-tyrosine), 8-hydroxy deoxyguanosine, (8-OH-dG) and RNS (3-nitrotyrosine).

Results and conclusions: HLE cell-line exhibited a bi-phasic response in terms of cell viability, ROS and RNS profiles. At doses <0.5?Gy, ROS and RNS levels were lower than control and at higher doses (>0.5?Gy) a steady increase was observed in each metabolite. This response was observed irrespective of dose-rate. Among the associations tested, cl, p, m-tyrosine and 3-nitrotyrosine revealed changes (p?相似文献   

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose:?Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate.

Materials and methods:?Non-tumour dose, D_nt, defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation.

Results:?An inverse correlation was found between D_nt and dose-rate of the radiation. D_nt increased 20-fold with decreasing dose-rate from 1–10^?8 Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger D_nt as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower D_nt levels.

Conclusions:?The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters.     

Enhanced transplantability of a cell line from a murine ovary granulosa cell tumour in syngeneic B6C3F1 mice continuously irradiated with low dose-rate gamma-rays

Purpose:?To understand the mechanisms of life-shortening due to early neoplastic death caused by chronic low dose-rate (LDR; 20 mGy/22 h/day) radiation which accumulates to a high dose (HD; 8 Gy) (LDR/HD) as reported previously.

Materials and methods:?Female B6C3F₁ mice were continuously exposed to LDR/HD gamma-rays under specific-pathogen-free (SPF) conditions for 400 days. OV3121 cells, which were derived from an ovarian granulosa cell tumour that arose in irradiated B6C3F₁ mice, were inoculated into LDR/HD irradiated and age-matched non-irradiated control mice. The transplantability of tumour cells as well as T cell subsets and the proliferative activities of T cells were compared between irradiated and non-irradiated mice.

Results:?We found that tumour formation of subcutaneously inoculated tumour cells occurred earlier in irradiated mice than in non-irradiated mice. Proliferative activity of draining lymph node lymphocytes against transplanted tumour cells as well as allogeneic mixed lymphocyte reactions were significantly reduced in irradiated mice compared to non-irradiated mice.

Conclusions:?These results suggest that decreased tumour-specific immune response due to LDR/HD irradiation may enhance tumorigenesis resulting in life-shortening of mice after chronic LDR/HD irradiation.     

Cytogenetic analysis in human lymphocytes after exposure to simulated cosmic radiation which reflects the inflight radiation environment.

PURPOSE: To determine the relative biological effectiveness (RBE) of a mixed neutron-gamma-radiation field and its high LET component on the induction of chromosome aberrations in human lymphocytes. MATERIALS AND METHODS: Human lymphocyte cultures were exposed in vitro to low doses of simulated cosmic radiation (2.39-5.81 mGy) at low dose rates (0.04-0.15 mGy/h). Chromosome aberrations, micronuclei, and sister chromatid exchanges (SCE) were analysed. The RBE for dicentric chromosomes was given in comparison to 60Co gamma-rays. RESULTS: For the induction of dicentric chromosomes by simulated cosmic radiation the RBE was up to 64, and up to 113 when calculating only the high LET component. The investigation of micronuclei and SCE showed no significant differences between controls and irradiated samples. CONCLUSIONS: Preliminary data indicate a high biological effectiveness of cosmic radiation and its neutron component in comparison with 60Co gamma-radiation.     

The effect of chronic radiation on the humoral immune response of rainbow trout (Onchorhynchus mykiss Walbaum).

Two separate experiments have examined the effect of exposing rainbow trout to chronic gamma-radiation, commencing immediately after fertilization. In experiment 1 the period of exposure extended for 20 days with groups receiving mean dose rates of 1.87, 3.73 and 9.03 mGy h-1, and mean total accumulated doses of 0.83, 1.66 and 4.01 Gy respectively. At 5 months of age fish were tested for specific antibody response to dinitrophenol coupled to keyhole limpet haemocyanin (DNP-KLH) and there was no significant difference in titre between irradiated groups and unirradiated controls. In experiment 2 the exposure period was extended to 246 days from fertilization. Mean dose-rates to the three groups used were the same as in the first experiment until hatching at 21 days and then lower with rates of 0.99, 1.9, and 4.66 mGy h-1 to the free-swimming fish. The mean total accumulated doses over the whole irradiation period were 5.43, 10.53 and 25.43 Gy respectively. The antibody response to DNP-KLH was significantly lower in trout receiving the highest dose-rate when compared with those of unirradiated controls or the lowest dose-rate group. The significance of these results is discussed in relation to radiation levels in areas of radioactive waste disposal, and results from a similar study published previously.     

Acute pulmonary and splenic response in an in vivo model of whole-body low-dose X-radiation exposure

Abstract

Purpose: Diagnostic radiation is an important part of patient care in the Intensive Care Unit; however, there is little data on the acute effects of exposure to these doses. We investigated pulmonary and splenic response 30?minutes, 4?hours or 24?hours after exposure to 2?mGy, 20?mGy, 200?mGy or 4?Gy whole-body X-radiation in a Sprague Dawley rat model.

Materials and methods: Lung injury was assessed via respiratory mechanics, pulmonary edema, cellular, and proteinaceous fluid infiltrate and protein expression of oxidative stress markers. The radiation effect on the spleen was determined via proliferation, apoptosis and protein expression of oxidative stress markers.

Results: All measurements of the lung did not differ from sham animals except for an increase in catalase after high dose exposure. Stimulated splenocyte proliferation increased after sham and low dose exposure, did not change after 200?mGy exposure and was significantly lower after 4?Gy exposure. The number of apoptotic cells increased 4?hours after 4?Gy exposure. There were fewer apoptotic cells after low dose exposure compared to sham. Both catalase and MnSOD were increased after 4?Gy exposure.

Conclusion: There was no measured effect on pulmonary function while there was an impact to the spleen after low and high dose exposure.     

60Co-γ射线全身低剂量率辐照对小鼠血浆中IL-12和IL-10的影响

目的研究低剂量电离辐射对小鼠免疫系统影响的剂量率效应。方法以^60Co-γ射线为辐照源，低、中和高3个辐射剂量（0．075、0．5、2．0Gy），恒定剂量率（0．5mGy／min）全身一次性照射小鼠，ELISA检测照射4h后血浆IL-12和IL-10的含量。结果低、中剂量照射后，血浆中IL-12、IL-10和IL-12／IL-10出现程度几乎相同地下降；但高剂量照射后，IL-12进一步显著下降，而IL-10上升至对照组水平，IL-12／IL-10比值进一步下降。结论恒定0．5mGy／min剂量率的^60Co-γ射线照射可损伤机体免疫功能，在0．075～0．5Gy剂量范围内损伤轻微，在2．0Gy时损伤明显，表明低剂量率电离辐射对免疫系统具有损伤作用。     

Cytogenetic Effects of Microwave Irradiation on Male Germ Cells of the Mouse

Summary

Hybrid male mice were exposed to 2·45 GHz microwaves for 30 min/day, 6 days a week for two consecutive weeks at power densities of 1·0, 100 or 400 W m^?2, with sham-exposed controls. Rectal temperatures before and after exposure were measured on days 1, 6 and 12. Measurements made on day 1 were treated with caution because of heterogeneity in rectal temperatures taken before exposure between the groups of mice given different treatments. On days 6 and 12, rectal temperatures rose by approximately 1°C in mice sham exposed, or exposed to 1 W m^?2 or 100 W m^?2. Only in the group of mice exposed to 400 W m^?2 was the mean rise in rectal temperature during exposure (about 3°C) significantly increased above the sham value. In groups killed 2–3 days after treatment (mainly meiotic exposure) frequencies of chromosome aberrations in spermatocytes showed no significant heterogeneity although the highest frequency of 1·5 per cent was at the highest (400 W m^?2 power density. Another group killed 30 days after 100 W m^?2 exposures (spermatogonial sampling) showed no significant increase over controls in chromosome aberration frequency. There was a small but significant increase in sperm count with increasing power density in mice killed 12–13 days after exposure, but a non-significant one in those exposed as spermatogonia (killed 41 days later). Thus effects were markedly less severe than those reported previously by Manikowska-Czerska et al. (1985) with a very similar radiation regime and were probably caused by the temperature enhancement.     

Chronic exposure to gamma irradiation at low-dose rates accelerates blood pressure decline associated with aging in female B6C3F1 mice

Abstract

Purpose: Many studies are focusing on the biological effects of gamma irradiation at low-dose rates. Studies have shown that chronic exposure to gamma irradiation at low-dose rates shortened the lifespan of mice due to neoplasm formation. The aim of this study was to clarify the physiological effects of long-term exposure to gamma irradiation at low-dose rates in mice, measured with noninvasive parameters such as blood pressure.

Materials and methods: Specific-pathogen-free female B6C3F₁ mice were irradiated with gamma rays at a low dose of 20 mGy/day – a dose rate shown to shorten the life span in previous studies. The blood pressure parameters (systolic, diastolic, and mean blood pressure), heart rate, tail blood volume, and blood flow of the mice were measured every 7 weeks. Age-matched, non-irradiated mice were used as controls.

Results and conclusion: The blood pressure levels of the irradiated mice decreased at an earlier age compared to the non-irradiated control mice. The expression levels of the marker genes of aging that are also associated with regulation of blood pressure showed significant differences between non-irradiated and irradiated mice. These results indicated that long-term exposure to gamma irradiation at low-dose rates induce the expression levels of Rap1a and reduces Panx1 and Sirt3, which may have contributed to the accelerated blood pressure decline in female mice.     

Expression of Cytoskeletal Elements in Proliferating Cells Following Radiation Exposure

Summary

Previous work has demonstrated that radiation exposure modulates the expression of a series of genes, including those that encode cytoskeletal elements. The experiments reported here were designed to examine (1) the comparative effects of neutrons administered at high versus low dose-rates, (2) the comparative effects of neutrons on cycling versus resting cells and (3) the comparative effects of neutrons versus γ-rays on β- and γ-actin mRNA accumulation in Syrian hamster embryo (SHE) cells 1 and 3 h post-irradiation. JANUS fission-spectrum neutrons from Argonne National Laboratory's JANUS reactor administered at high (12 cGy/min) dose-rates had little effect on resting cells, but at very low dose-rates (0·1 cGy/min) had a repressive effect on γ-actin mRNA accumulation. Increased accumulation of β-actin mRNA was detected following the exposure of cells to neutrons administered at high dose-rates, but repression of β-actin mRNA was observed when neutrons were administered at low dose-rates. Cycling cells (unexposed and neutron irradiated) in all cases expressed higher levels of all actin-specific mRNAs than resting cells; β-actin mRNA (but not γ-actin mRNA) was induced to a greater extent in cycling cells than in resting cells during the first hour following neutron exposure. In resting cells, however, low dose-rate neutrons were more effective than low dose-rate γ-rays at repressing both γ- and β-actin mRNA accumulation. These results demonstrate the differential effects of radiation quality (neutrons versus γ-rays) and cell-cycle state on the modulation of actin isotype-specific gene expression.     

Radiation necrosis of the brain: Time of onset and incidence related to total dose and fractionation of radiation

Summary Clinical deterioration during or after brain irradiation may be due to progression of neoplasm or radiation induced necrosis of the neoplasm and/or of normal brain tissues, or a combination of all. Eight patients with histologically documented radiation induced lesions of the brain are included in this study. The radiation therapy included the fractional schedule, group A, who received 280 to 300 rads daily, to a total dose of 4500 to 5000 rads and weekly exposure did not exceed 900 rads. Group B patients were exposed to 850 rads, daily dose on day 1, 3, 21 and 23 to a total dose of 3400 rads. The incidence of radiation induced lesions of brain was 3.4% in patients group A and 8.7% in group B patients (without) statistical significance). The median time of onset of these lesions after completion of radiation therapy was significantly shorter in group B patients (8.5 months) as opposed to group A patients (21 months).     

Expression of cytoskeletal elements in proliferating cells following radiation exposure.

Previous work has demonstrated that radiation exposure modulates the expression of a series of genes, including those that encode cytoskeletal elements. The experiments reported here were designed to examine (1) the comparative effects of neutrons administered at high versus low dose-rates, (2) the comparative effects of neutrons on cycling versus resting cells and (3) the comparative effects of neutrons versus gamma-rays on beta- and gamma-actin mRNA accumulation in Syrian hamster embryo (SHE) cells 1 and 3 h post-irradiation. JANUS fission-spectrum neutrons from Argonne National Laboratory's JANUS reactor administered at high (12 cGy/min) dose-rates had little effect on resting cells, but at very low dose-rates (0.1 cGy/min) had a repressive effect on gamma-actin mRNA accumulation. Increased accumulation of beta-actin mRNA was detected following the exposure of cells to neutrons administered at high dose-rates, but repression of beta-actin mRNA was observed when neutrons were administered at low dose-rates. Cycling cells (unexposed and neutron irradiated) in all cases expressed higher levels of all actin-specific mRNAs than resting cells; beta-actin mRNA (but not gamma-actin mRNA) was induced to a greater extent in cycling cells than in resting cells during the first hour following neutron exposure. In resting cells, however, low dose-rate neutrons were more effective than low dose-rate gamma-rays at repressing both gamma- and beta-actin mRNA accumulation. These results demonstrate the differential effects of radiation quality (neutrons versus gamma-rays) and cell-cycle state on the modulation of actin isotype-specific gene expression.     

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate. Materials and methods: Non-tumour dose, D(nt), defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation. Results: An inverse correlation was found between D(nt) and dose-rate of the radiation. D(nt) increased 20-fold with decreasing dose-rate from 1-10(-8) Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger D(nt) as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower D(nt) levels. Conclusions: The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters.     

Exposure factors and screen-film combinations in temporomandibular joint radiography

Exposure factors and screen-film combinations providing optimal quality are identified for transcranial and transpharyngeal temporomandibular joint views, using conventional intra-oral radiographic equipment without grids. Standardized transcranial and transpharyngeal views, using a fixed whole cadaver head, were performed. Ten readily available screen-film combinations, ranging in nominal speed 20-600, were exposed over 40-100 kV. Films were blindly and independently order ranked by three observers on the basis of sharpness and contrast of cortical outline, trabecular detail, and visualization of adjacent bony structures. Preferred screen-film combinations as a function of kV, preferred kV levels for each screen-film combination, and overall ranking irrespective of kV or screen-film combination, were established. Accepting the use of the lowest radiation dose possible for diagnostically useful radiographs but imposing arbitrarily an upper limit of 20 mGy, it was found that exposures between 50 kV and 70 kV gave the optimal result for both techniques. The amount of scattered radiation in the emergent beam differs greatly between the two techniques. The most favoured combinations for the transpharyngeal technique used screens of fine resolution. Min-r/ortho M screen and film with nominal speed 40 at 60 kV gave 8.0 mGy skin dosage at 0.8 seconds exposure; the same combination at 50 kV was the most favoured, but with skin dosage calculated at 16.7 mGy for 3.0 seconds exposure. For the transcranial technique, medium speed screens providing better differentiation of scattered radiation beams and increased speeds were preferred. Most favoured for image quality was the Lanex Fine/T-Mat G combination at 60 kV giving 17.5 mGy skin radiation dose at 1.75 seconds exposure.(ABSTRACT TRUNCATED AT 250 WORDS)