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PubMed1997

Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk.

BACKGROUND: As a part of multimodality therapy, many patients with tumors of the trunk receive radiation therapy. The major morbidity of this therapy is often secondary to incidental radiation damage to tissues adjacent to treatment areas. METHODS: We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. RESULTS: Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. CONCLUSION: We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites.

Abdominal Muscles↗

PubMed1999

[Long-term radiation damage to the skin and eye after combined beta- and gamma- radiation exposure during the reactor accident in Chernobyl].

BACKGROUND: In April 1986, numerous reactor workers and firemen were exposed to high doses of ionizing radiation during the Chernobyl nuclear power plant accident. Apart from high ambient gamma-ray exposures they received inhomogeneous contamination with beta-rays from fission products, resulting in severe skin exposure. PATIENTS AND METHODS: Sixteen of these so called Liquidators were repeatedly examined between 1991 and 1996. Their doses ranged from 0.35 to 9 Gy, partly confirmed by determination of chromosomal aberrations. Ophthalmologic examination included non-subjective assessment of lenticular radiation damage with an electronic Scheimpflug camera system. Digital image analysis allowed the comparison of opacification units to previous and normal findings. RESULTS: Four Liquidators had posterior subcapsular opacifications in different degrees, one presented only after cataract extraction. One patient had dense corticonuclear cataracts and pseudoexfoliation-like changes. Three men had severe dry eye syndrome. Eight men had no ocular complications. Retinal radiation damages were absent. 15 Liquidators suffered from severe chronic cutaneous radiation damage, which led to amputations in 3 cases. CONCLUSIONS: A relation between ocular and dermatological findings was not expected and could, in fact, not be seen. The comparison of posterior subcapsular opacification and doses revealed no distinct relation, although it indicates a correlation that is here not quantified. The doses represent organ doses for the bone marrow which is primarily exposed to deeper penetrating gamma-radiation. Thus they need not be correlated with combined beta- and gamma-doses in organs such as skin and eye because the superficial exposure due to beta-radiation may differ greatly form the whole body exposure as reflected in bone marrow doses.

Accidents, Occupational↗

PubMed2004

Radiation protection aspects of the cosmic radiation exposure of aircraft crew.

Aircraft crew and frequent flyers are exposed to elevated levels of cosmic radiation of galactic and solar origin and secondary radiation produced in the atmosphere, the aircraft structure and its contents. Following recommendations of the International Commission on Radiological Protection in Publication 60, the European Union introduced a revised Basic Safety Standards Directive, which included exposure to natural sources of ionising radiation, including cosmic radiation, as occupational exposure. The revised Directive has been incorporated into laws and regulations in the European Union Member States. Where the assessment of the occupational exposure of aircraft crew is necessary, the preferred approach to monitoring is by the recording of staff flying times and calculated route doses. Route doses are to be validated by measurements. This paper gives the general background, and considers the radiation protection aspects of the cosmic radiation exposure of aircraft crew, with the focus on the situation in Europe.

Aircraft↗

PubMed2002

Physical and chemical considerations of damage induced in protein crystals by synchrotron radiation: a radiation chemical perspective.

Radiation-induced degradation of protein or DNA samples by synchrotron radiation is an inherent problem in X-ray crystallography, especially at the 'brighter' light sources. This short review gives a radiation chemical perspective on some of the physical and chemical processes that need to be considered in understanding potential pathways leading to the gradual degradation of the samples. Under the conditions used for X-ray crystallography at a temperature of <100 K in the presence of cryoprotectant agents, the majority of radiation damage of the protein samples arises from direct ionization of the amino acid residues and their associated water molecules. Some of the chemical processes that may occur at these protein centres, such as bond scission, are discussed. Several approaches are discussed that may reduce radiation damage, using agents known from radiation chemistry to minimize radical-induced degradation of the sample.

Crystallization↗

PubMed2005

Dose-dependent generation of RET/PTC in human thyroid cells after in vitro exposure to gamma-radiation: a model of carcinogenic chromosomal rearrangement induced by ionizing radiation.

Ionizing radiation is a well-known risk factor for thyroid cancer in human populations. Chromosomal rearrangements involving the RET gene, known as RET/PTC, are prevalent in thyroid papillary carcinomas from patients with radiation history. We studied the generation of RET/PTC in HTori-3 immortalized human thyroid cells exposed to a range of doses of gamma-radiation and harvested 2, 5-6, and 9 d later. RET/PTC1 and RET/PTC3 were detected by RT-PCR followed by Southern blotting and hybridization with internal oligonucleotide probes. No RET/PTC was found in cells harvested 2 and 5-6 d after irradiation, whereas 59 RET/PTC events were detected in cells collected 9 d after exposure. The average rate of RET/PTC induction was 0.1 x 10(-6) after exposure to 0.1 Gy, 1.6 x 10(-6) after 1 Gy, 3.0 x 10(-6) after 5 Gy, and 0.9 x 10(-6) after 10 Gy. When adjusted for cell survival, the rate after 10 Gy was comparable with those after 5 Gy. RET/PTC1 was more common than RET/PTC3 after each dose, comprising 80% of all rearrangements. In this study, we demonstrate a dose-dependent induction of RET/PTC rearrangements in human thyroid cells after exposure to 0.1-10 Gy gamma-radiation. This provides additional evidence for a direct link between this genetic event and radiation exposure and offers a powerful experimental system for studying radiation-induced carcinogenesis in the thyroid gland.

Cell Proliferation↗

PubMed1993

Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid.

The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. We have identified 4296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3843 subjects. Of the 2634 subjects who have been found, 1043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and our screening program, which began in 1974, we compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.

Adult↗

PubMed2002

Molecular targets in cellular response to ionizing radiation and implications in space radiation protection.

DNA repair systems and cell cycle checkpoints closely co-operate in the attempt of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA double-strand breaks (DSB) are considered as the most biologically important radiation-induced damage. Their spatial distribution and association with other types of damage depend on radiation quality. It is believed these features affect damage reparability, thus explaining the higher efficiency for cellular effects of densely ionizing radiation with respect to gamma-rays. DSB repair systems identified in mammalian cells are homologous recombination (HR), single-strand annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may participate in more than one of these repair systems. DNA damage also triggers biochemical signals activating checkpoints responsible for delay in cell cycle progression that allows more time for repair. Those at G1/S and S phases prevent replication of damaged DNA and those at G2/M phase prevent segregation of changed chromosomes. Individuals with lack or alterations of genes involved in DNA DSB repair and cell cycle checkpoints exhibit syndromes characterized by genome instability and predisposition to cancer. Information reviewed in this paper on the basic mechanisms of cellular response to ionizing radiation indicates their importance for a number of issues relevant to protection of astronauts from space radiation.

Animals↗

PubMed2006

Radiation sensitivity of GL261 murine glioma model and enhanced radiation response by flavopiridol.

Response of a solid tumor to radiation treatment depends, in part, on the intrinsic radiosensitivity of tumor cells, the proliferation rate of tumor cells between radiation treatments and the hypoxic state of the tumor cells. A successful radiosensitizing agent would target S-phase cells and hypoxia. Recently, we demonstrated the anti-tumor effects of flavopiridol in the GL261 murine glioma model might involve 1) recruitment of tumor cells to S-phase (Newcomb et al Cell Cycle 2004; 3:230-234) and 2) an anti-angiogenic effect on the tumor vasculature by downregulation of hypoxia-inducible factor -1alpha (HIF-1alpha) (Newcomb et al Neuro-Oncology 2005; 7:225-235). Given that flavopiridol has demonstrated radiosensitizing activity in several murine tumor models, we tested whether it would enhance the response of GL261 tumors to radiation. In the present study, we evaluated the intrinsic radiation sensitivity of the GL261 glioma model using the tumor control/cure dose of radiation assay (TCD(50)). We found that a single dose of 65 Gy (CI 57.1-73.1) was required to cure 50% of the tumors locally. Using the tumor growth delay assay, fractionated radiation (5 fractions of 5 Gy over 10 days) combined with flavopiridol (5 mg/kg) given three times weekly for 3 cycles produced a significant growth delay. Our results indicate that the GL261 murine glioma model mimics the radioresistance encountered in human gliomas, and thus should prove useful in identifying promising new investigational radiosensitizers for use in the treatment of glioma patients.

Animals↗

PubMed1999

[Contribution of radiation biology to the development of radiation therapy].

Results of radiation therapy for malignant tumors have steadily improved, and both radiation biology and radiation physics have contributed to this improvement. As examples of such contribution, radiobiologically-elaborated continuous hyperfractionated accelerated radiotherapy (CHART) has been proven to be superior to conventional radiotherapy against non-small cell lung cancer, and a hypoxic cell sensitizer nimorazole has been proven to be effective against pharyngeal and supraglottic laryngeal cancers. Based on laboratory studies, a combination of chemotherapy and radiotherapy has been shown to be superior to radiotherapy alone in many cancers. Radiation biology has also provided important fundamental data for clinical applications of heavy ion and proton beam therapy. In the future, useful predictive assays and radioprotectors are also expected to be developed. Radiation biology should continue to contribute to the further development of clinical radiation therapy.

Antineoplastic Agents↗

PubMed2002

Cytokine-based treatment of radiation injury: potential benefits after low-level radiation exposure.

The use of growth factors (GFs) in the treatment of radiation injury has focused on enhancing recovery from acute radiation syndrome. A number of new GFs have shown significant in vivo and in vitro preclinical efficacy; some of these have recently been approved by the Food and Drug Administration, some are in various phases of clinical trials, and some are moving through preclinical evaluations. The most promising new GFs in the context of enhancing the viability of irradiated hematopoietic stem cells (HSCs) are flt-3L, c-kitL, and c-mplL. These GFs, as well as interleukin 3 (IL-3), have been shown to maintain viability, suppress apoptosis, and promote the clonal growth of primitive murine and human hematopoietic progenitor cells. Further evidence suggests that these GFs may also act in synergy with each other. Additionally, three families of chimeric proteins that consist of dual GF receptor (R) agonists have been engineered: myelopoietin, promegapoietin, and progenipoietin. These proteins activate the IL-3 and granulocyte colony-stimulating factor Rs, the IL-3 and mpl Rs, and the flt-3L and granulocyte colony-stimulating factor Rs, respectively. The preclinical data indicate that the chimeric GFR agonists are potent stimulators of hematopoiesis in myelosuppressed nonhuman primates and can effectively alleviate acute radiation syndrome in animals. Acute or protracted low-level radiation exposure does not require the extensive clinical care necessary following radiation-induced myelosuppression. The main question is whether these new GFs will allow for enhanced repair of radiation-induced chromosome aberrations while promoting early survival of HSCs. Other questions include the following: Will an early, brief exposure to GFs suppress p53-dependent apoptosis and induce expression of bcl-2 with a concomitant enhancement of DNA repair capacity? What is the effect of GF stimulation of irradiated HSCs on p53 cell cycle checkpoint activity? Will GFs promote survival of "transformed" cells that would otherwise be eliminated by p53 activation of apoptosis-promoting genes? Relevant animal models and access to appropriate GFs will be required to answer these questions.

Animals↗

PubMed1983

Radiation biology: the conceptual and practical impact on radiation therapy.

Radiation biology has had an important impact on clinical radiation therapy by providing a rationale for implementation of new treatment strategies and for clinical concepts or practices thereby increasing their acceptance. The observed rather narrow range of D0 and n values for mammalian cells contributed to successful trials of radiation treatment of several "radiation-resistant" tumors, e.g., carcinoma of prostate, color-rectum, and sarcoma of soft tissue. Attention of clinicians was forcibly directed to assessment of local results (local failure, treatment complications) and not merely survival at 5 years by the extensive literature of cell survival curves (in vivo and in vitro) and dose-response assays on normal and tumor tissues. Upon these same laboratory results a scientific rationale was developed for use of shrinking field technique, low dose for subclinical disease, and the combination of moderate dose radiation therapy and conservative surgery. The entire area of clinical research into altered dose fractionation schedules is based upon research on cell proliferation kinetics and repair of radiation damage. The understanding that the time for complete regression of tumor depends not only upon cell kill but also on the pattern of cell proliferation of the progeny of lethally irradiated cells and the abundance of stroma provided a basis for accepting patients with slowly responding tumors for treatment. There remains a wide field of need in research in this area as even today a large proportion of patients who die of cancer die with their cancer uncontrolled at the primary site.

Adult↗

PubMed1995

Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy.

BACKGROUND: Primary hyperparathyroidism (HPT) occurs more frequently in persons who have been exposed to low-dose therapeutic radiation. Little information is available concerning whether or not the clinical, metabolic, and pathologic manifestations, as well as outcome, differ in these patients when compared with patients with sporadic HPT. STUDY DESIGN: Records from 438 unselected patients with primary HPT, who were treated from 1982 to 1993 were retrospectively analyzed. All patients prospectively received a standard questionnaire preoperatively and postoperatively concerning clinical manifestations and a history of radiation exposure. Forty-nine patients had a history of radiation exposure (rHPT), whereas 389 did not have sporadic HPT (sHPT). RESULTS: There was no difference in gender (36 women and 13 men versus 289 women and 100 men) or age (mean of 52 +/- 12 versus 57 +/- 16 years) in patients with rHPT or sHPT. Fatigue, neuropsychiatric disorders, memory loss, nocturia, and polyurea were more common in patients with sHPT (p < 0.05), whereas pain in joints was more common in patients with rHPT (63 versus 52 percent; p < 0.001). Serum calcium levels were similar (11.1 +/- 0.8 versus 11.2 +/- 0.8 mg per dL), but serum parathyroid hormone levels were higher in rHPT (448 +/- 14 percent of upper limit of normal versus 371 +/- 12 percent upper limit of normal). The parathyroid pathology was similar in the two groups (single adenoma 74 versus 72 percent, hyperplasia 14 versus 16 percent, and double adenoma 12 versus 12 percent in rHPT versus sHPT, respectively). Thyroid pathology was more common in the rHPT group (multinodular goiter 27 versus 7 percent and papillary thyroid carcinoma 14 versus 0.3 percent). Seven (1.8 percent) of patients not receiving radiation therapy treated by us had persistent HPT, but no patients receiving or not receiving radiation therapy had recurrent HPT during the follow-up period (six years). CONCLUSIONS: Patients who have HPT after radiation treatment have more thyroid neoplasms but are otherwise quite similar to other patients with primary hyperparathyroidism.

Adolescent↗

PubMed1975

Final report of the Advisory Committee for Radiation Biology Aspects of the SST: cosmic radiation exposure in supersonic and subsonic flight.

The main body of this document consists of four major sections: A) An introduction describing the scope of Committee operations and providing a brief exposition of the concepts of radiation protection; B) A survey of experimental and theoretical data on cosmic radiations that have been obtained in individual research projects with emphasis on investigations that were performed under the sponsorship of the Committee. The studies evaluate galactic and solar radiation as a function of altitude and magnetic latitude; C) Best current estimates of cosmic radiation levels in the atmosphere; and D) Radiation protection recommendations dealing with maximum permissible doses and operational aspects covering satellite warning systems, on-board instrumentation, and forecasting. Nine annexes submitted by individual authors cover various of these subjects in greater detail.

Aerospace Medicine↗

PubMedDate not supplied

Ionizing radiation and the conceptus: neurophysiologic effects of prenatal X-radiation on offspring.

A brief review of the literature precedes the presentation of a radiation behavioral teratology study. The various types of radiation and the units of measure used in radiation biology are discussed. The concept of the radiation-induced teratogenic "triad" of growth retardation, malformation, and death is presented. A discussion of stage- and dose-dependent sensitivity to prenatal irradiation is followed by an introduction to behavioral teratology as a new interdisciplinary area of investigation, emphasizing postnatal psychophysiologic analyses of the effects of prenatal exposure. In the present study, rats were exposed to an acute dosage level of 0.6 Gy (60 RAD) X-radiation on day 9 or 17 of gestation. The neonates were given five neonatal reflex tests, observed for the appearance of four physiologic markers, and, as young adults, subjected to three of six behavioral tests. The irradiated offspring exhibited retarded postnatal growth and altered reflex and behavioral activity. These results indicate that irradiation at a dosage level which does not cause overt morphologic malformations at birth does result in altered postnatal growth and psychophysiologic development.

Abnormalities, Radiation-Induced↗

PubMed1999

Radiation protection concepts and quantities for the occupational exposure to cosmic radiation.

For the purposes of dose limitation and dose control, the harm, or detriment, of exposure to radiation is assessed by the quantity effective dose. Effective dose is evaluated by the application of factors to the averaged absorbed dose in the organs and tissues of the body. Radiation monitoring instruments are generally calibrated in terms of the quantity ambient dose equivalent which is defined in a simple spherical phantom. The relationship of these quantities is described. Requirements for the radiation protection of aircraft crew are given in the European Union Council Directive 96/29/EURATOM. There are requirements to assess the exposure of aircraft crew, to inform them of health risks, to reduce higher doses, and to control the dose to the fetus. There are no explicit dose limits, other than a dose objective to be applied to the exposure of the fetus, and no requirements for designation of areas or classification of workers. There are significant differences between the exposure condition of aircraft crew and workers in most other industries where there is occupational exposure to radiation. There are greater ranges of radiation types and energy, and there are different dose distributions and characteristics of the working populations. However, the field intensity is predictable and, with the exception of rare solar events, there is no risk of significant unexpected exposures. Dose assessment is anticipated to be by folding staff roster information with estimates of route doses, since there is little variability of dose rate within an aircraft. Route doses, which may be either an agreed average value for a given airport pairing and aircraft type, or be flight specific, will be closely linked to measured values. Requirements as to the accuracy of dose assessment should be applied which are broadly similar to those used in individual monitoring generally.

Aerospace Medicine↗

PubMed2005

Characterisation of ionisation chambers for a mixed radiation field and investigation of their suitability as radiation monitors for the LHC.

Monitoring of the radiation environment is one of the key tasks in operating a high-energy accelerator such as the Large Hadron Collider (LHC). The radiation fields consist of neutrons, charged hadrons as well as photons and electrons with energy spectra extending from those of thermal neutrons up to several hundreds of GeV. The requirements for measuring the dose equivalent in such a field are different from standard uses and it is thus necessary to investigate the response of monitoring devices thoroughly before the implementation of a monitoring system can be conducted. For the LHC, it is currently foreseen to install argon- and hydrogen-filled high-pressure ionisation chambers as radiation monitors of mixed fields. So far their response to these fields was poorly understood and, therefore, further investigation was necessary to prove that they can serve their function well enough. In this study, ionisation chambers of type IG5 (Centronic Ltd) were characterised by simulating their response functions by means of detailed FLUKA calculations as well as by calibration measurements for photons and neutrons at fixed energies. The latter results were used to obtain a better understanding and validation of the FLUKA simulations. Tests were also conducted at the CERF facility at CERN in order to compare the results with simulations of the response in a mixed radiation field. It is demonstrated that these detectors can be characterised sufficiently enough to serve their function as radiation monitors for the LHC.

Computer-Aided Design↗

PubMed1964

RADIATION PROTECTION IN CANADA. III. THE ROLE OF THE RADIATION PROTECTION DIVISION IN SAFEGUARDING THE HEALTH OF THE PUBLIC.

The current status of radiation protection in Canada is discussed in the last of a three-part series. Particular emphasis has been placed on the role of the Radiation Protection Division of the Department of National Health and Welfare. A radioactive fallout study program has been established involving the systematic collection of air and precipitation samples from 24 locations, soil samples from 23 locations, fresh-milk samples from 16 locations, wheat samples from nine areas and human-bone specimens from various hospitals throughout Canada. A whole-body-counting facility and a special study of fallout in Northern areas have also been initiated. For any age group, the highest average strontium-90 concentration in human bone so far reported has been less than four picocuries per gram of calcium compared with the maximum permissible level of 67 derived from the International Committee on Radiation Protection (ICRP) recommendations. By the end of 1963 a general downward trend of levels of radioactivity detected in other parts of the program has been observed. Programs to assess the contribution to the radiation exposure of members of the population from medical x-rays, nuclear reactor operations and natural background-radiation sources have also been described. The annual genetically significant dose from diagnostic x-ray examinations in Canadian public hospitals has been estimated to be 25.8 mrem. Results from the reactor-environment monitoring programs have not suggested the presence of radioactivity beyond that contributed from fallout.

Air Pollution↗

PubMed1994

Radiation hormesis in relation to radiation protection.

A radiation-induced adaptive response has been convincingly demonstrated in a variety of cultured cells. It is associated with the activation of genes and the up-regulation of protein enzymes, resulting in a delay in cell-cycling and the opportunity to repair radiation-damaged DNA as a transient phenomenon. Just how the adaptive response operates in a multi-cellular organism is still obscure, but there is little or no evidence in rodents and the beagle dog of a shortening of lifespan after exposure to acute doses up to a few hundreds of mGy or after chronic daily exposure resulting in accumulated doses of up to a few Gy. Nevertheless there is an increase in both non-neoplastic and neoplastic diseases which need not be life-threatening. A prudent approach has been used by the ICRP in deriving a value for radiation-induced detriment at low doses from which to recommend individual dose and risk limits in their system of radiological protection. This is not to deny the possible existence of an adaptive response. However, in the opinion of the author, there is no overwhelming evidence to date which justifies the belief that exposure to low doses in the range of natural background up to a few tens of mSv reduces the incidence of radiation-induced cancer in a population composed of persons of all ages with a wide spectrum of diseases and with widely different sensitivities to radiation.

Adaptation, Physiological↗