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Journal ArticleDOI

Long-term immune and cytogenetic effects of high level natural radiation on Ramsar inhabitants in Iran

01 Jan 2004-Journal of Environmental Radioactivity (Elsevier)-Vol. 74, Iss: 1, pp 107-116

TL;DR: Research in Ramsar, a northern coastal city of Iran, has some high level natural radiation areas (HLNRAs) as well as over 50 hot springs with low and high radium contents used as spas by the public and vacationers, and shows significant increase of CD69 expression on TCD4+ stimulated cells and total serum IgE and higher incidence of stable and unstable chromosomal aberrations in the HLNRA group compared to the control group with normal background radiation.

AbstractRamsar, a northern coastal city of Iran, overlooking the Caspian Sea, has some high level natural radiation areas (HLNRAs) as well as over 50 hot springs with low and high radium contents used as spas by the public and vacationers. The average whole body dose received by population in these areas is about 5 times higher than the normal background radiation level. Studies on the long-term effects of high level natural radioactivity on some immunological and cytogenetical parameters, in the Ramsar inhabitants are summarized in this paper. Our results showed a significant increase of CD69 expression on TCD4+ stimulated cells (P < 0.004) and a significant increase of total serum IgE (P < 0.05), and also higher incidence of stable and unstable chromosomal aberrations in the HLNRA group compared to the control group with normal background radiation (P < 0.05).Other humoral immune parameters, did not show significant differences between the two groups.

Topics: Population (52%), Environmental exposure (52%)

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Journal ArticleDOI
TL;DR: Estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence are provided and it appears that the rate of dose delivery does not modify the low incidence for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease.
Abstract: This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

890 citations


Cites background from "Long-term immune and cytogenetic ef..."

  • ..., 2007), as well as a significant increase in immunoglobulin E (Ghiassi-nejad et al., 2004), which is indicative of the prevalence of the humoral immune response over the cellular response....

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01 Jan 2012
Abstract: GUEST EDITORIAL PART I: ICRP STATEMENT ON TISSUE REACTIONS PART II: EARLY AND LATE EFFECTS OF RADIATION IN NORMAL TISSUES AND ORGANS - THRESHOLD DOSES FOR TISSUE REACTIONS IN A RADIATION PROTECTION CONTEXT ABSTRACT PREFACE EXECUTIVE SUMMARY GLOSSARY 1. INTRODUCTION 1.1. Purpose of report 1.2. Definition and nature of tissue reactions to ionising radiation 1.3. General principles of radiation effects in cells and tissues 1.4. References 2. RESPONSE OF TISSUES AND ORGANS TO RADIATION 2.1. Haematopoietic and immune systems 2.2. Digestive system 2.3. Reproductive system 2.4. Skin 2.5. Cardiovascular and cerebrovascular systems 2.6. Eye 2.7. Respiratory system 2.8. Urinary tract 2.9. Musculoskeletal system 2.10. Endocrine system 2.11. Nervous system 2.12. References 3. MODIFIERS OF NORMAL TISSUE RESPONSE 3.1. Terminology 3.2. Mechanisms of action 3.3. Influence of modifiers on radiation response in tissue 3.4. References 4. THRESHOLD DOSES IN RELATION TO RADIOSENSITIVITY OF ORGANS AND TISSUES 4.1. Introduction 4.2. Haematopoietic and immune systems 4.3. Digestive system 4.4. Reproductive system 4.5. Skin 4.6. Cardiovascular and cerebrovascular systems 4.7. Eye 4.8. Respiratory system 4.9. Urinary tract 4.10. Musculoskeletal system 4.11. Endocrine system 4.12. Nervous system 4.13. Conclusions 4.14. References ANNEX A. SUMMARY OF STUDIES OF EXPOSURE AND OPACITIES OR CATARACTS

800 citations


Journal ArticleDOI
TL;DR: The possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation is reviewed.
Abstract: Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.

210 citations


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Journal ArticleDOI
TL;DR: Although adaptive response seems to function by an on/off principle, it is a phenomenon showing a high degree of inter- and intraindividual variability, it remains to be seen to what extent adaptive response is functional in humans at relevant dose and dose-rate exposures.
Abstract: Radiation-induced adaptive response belongs to the group of non-targeted effects that do not require direct exposure of the cell nucleus by radiation. It is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. Adaptive responses have been observed in vitro and in vivo using various indicators of cellular damage, such as cell lethality, chromosomal aberrations, mutation induction, radiosensitivity, and DNA repair. Adaptive response can be divided into three successive biological phenomena, the intracellular response, the extracellular signal, and the maintenance. The intracellular response leading to adaptation of a single cell is a complex biological process including induction or suppression of gene groups. An extracellular signal, the nature of which is unknown, may be sent by the affected cell to neighbouring cells causing them to adapt as well. This occurs either by a release of diffusible signalling molecules or by gap-junction intercellular communication. Adaptive response can be maintained for periods ranging from of a few hours to several months. Constantly increased levels of reactive oxygen species (ROS) or nitric oxide (NO) have been observed in adapted cells and both factors may play a role in the maintenance process. Although adaptive response seems to function by an on/off principle, it is a phenomenon showing a high degree of inter- and intraindividual variability. It remains to be seen to what extent adaptive response is functional in humans at relevant dose and dose-rate exposures. A better understanding of adaptive response and other non-targeted effects is needed before they can be confirmed as risk estimate factors for the human population at low levels of ionising radiation.

145 citations


Cites background from "Long-term immune and cytogenetic ef..."

  • ...serum IgE indicating an induction of the immune response [ 40 ]....

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Journal ArticleDOI
TL;DR: These studies suggest that current levels of natural radioactivity may affect mutational input and thereby the genetic constitution and composition of natural populations, and a concerted effort to address this lack of research should be made.
Abstract: Natural levels of radioactivity on the Earth vary by more than a thousand-fold; this spatial heterogeneity may suffice to create heterogeneous effects on physiology, mutation and selection. We review the literature on the relationship between variation in natural levels of radioactivity and evolution. First, we consider the effects of natural levels of radiation on mutations, DNA repair and genetics. A total of 46 studies with 373 effect size estimates revealed a small, but highly significant mean effect that was independent of adjustment for publication bias. Second, we found different mean effect sizes when studies were based on broad categories like physiology, immunology and disease frequency; mean weighted effect sizes were larger for studies of plants than animals, and larger in studies conducted in areas with higher levels of radiation. Third, these negative effects of radiation on mutations, immunology and life history are inconsistent with a general role of hormetic positive effects of radiation on living organisms. Fourth, we reviewed studies of radiation resistance among taxa. These studies suggest that current levels of natural radioactivity may affect mutational input and thereby the genetic constitution and composition of natural populations. Susceptibility to radiation varied among taxa, and several studies provided evidence of differences in susceptibility among populations or strains. Crucially, however, these studies are few and scattered, suggesting that a concerted effort to address this lack of research should be made.

106 citations


References
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01 Jan 2000
TL;DR: This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices, in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation.
Abstract: NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

3,693 citations


Journal Article
TL;DR: The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer.
Abstract: An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.

513 citations


"Long-term immune and cytogenetic ef..." refers background in this paper

  • ...More recently, it has been suggested that chromosome aberration frequency is itself an indicator of cancer risk rather than just a reflection of exposure (Hagmar et al., 1994; Bonassi et al., 2000)....

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Journal Article
TL;DR: An increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk in peripheral blood lymphocytes, according to an ongoing Nordic cohort study of cancer incidence.
Abstract: Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.

505 citations


"Long-term immune and cytogenetic ef..." refers background in this paper

  • ...More recently, it has been suggested that chromosome aberration frequency is itself an indicator of cancer risk rather than just a reflection of exposure (Hagmar et al., 1994; Bonassi et al., 2000)....

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Journal ArticleDOI
TL;DR: Current understanding of the mechanisms involved in IgE regulation are summarized in this paper, which is of primary importance in defining alterations responsible for the pathological conditions characterized by hyperproduction of IgE.
Abstract: The IgE antibody system is among the most sophisticated of immune defense mechanisms. IgE molecules bind specifically and avidly to receptors localized on the surface of tissue mast cells and circulating basophils. These cells can produce and release several potent mediators after antigen interaction with a small number of surface-bound IgE molecules. The enormous amplification power of the IgE antibody system not only provides an important defense mechanism against parasites, but is also responsible for a number of clinical disorders. The human pathological condition most commonly associated with hyperproduction of IJE is atopy, the familial allergic disorder of immediate-type hypersensitivity to environmental allergens. In this paper Sergio Romagnani summarizes current understanding of the mechanisms involved in IgE regulation. Such studies are of primary importance in defining alterations responsible for the pathological conditions characterized by hyperproduction of IgE.

255 citations


"Long-term immune and cytogenetic ef..." refers background in this paper

  • ...Romagnani (1990) reported that the Th2 lymphocytes are more radioresistant than other lymphocytes and IL-4 produced by these cells, enhance IgE production....

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