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To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a D' of 0.928 (r2 = 0.581) for -808 T>C and -19 C>T, 0.928 (r2 = 0.581) for -797 G>A and -19 C>T in Han Chinese HBRA residents. Complete LD with a D' of 1.0 (r2 = 1.0) was observed between -808 T>C and -797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (-637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying -19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the -19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.

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Surface deposits of rare earth element (REE) were identified in the Bat Xat district, Northern Vietnam. As the area is inhabited, an in-depth investigation was carried out to assess the radioactivity levels and to evaluate the radiation exposure and radiological risks for the population. Samples of REE ore, soils, water and several foods locally produced were collected and analyzed by gamma spectrometry for determination of 232Th, 226Ra, and 40 K. Radon (222Rn and 220Rn) measurements were carried out in dwellings at the villages located near by the REE deposit area, and in Hanoi for comparison. Based on the measured radionuclide concentrations, several radiological parameters were calculated to evaluate the radiological risks for the population and to compare with worldwide values. Results indicate that the representative person of the most exposed group living near the REE deposits may receive a total annual effective dose as high as 37.9 ± 10.6 mSv, i.e., approximately 16 times the world average dose of 2.4 mSv y-1. Consequently, this area should be considered a high background radiation area. Exposure to external radiation and internal radiation from ingestion and inhalation of radionuclides were assessed separately. Radon inhalation contributed to approximately 70% of the total annual effective dose, with both radon isotopes contributing significantly, while the ingestion of local foods and water gave minor contributions to the total effective dose. Several measures were considered to improve the radiation safety and recommendations are given to relocate the most exposed members of the population.

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Purpose: A population-based case-control study was conducted in Yangjiang and Enping areas in South China to assess whether the risk of lens opacity induced by natural high background radiation exposure is modulated by polymorphisms of ATM and TP53.Materials and methods: A total of 133 cases who were diagnosed with cortical and posterior subcapsular (PSC) opacity were recruited, and 419 healthy controls were selected through counter-matching in terms of radiation status. Genomic DNA from all the participants was genotyped with the Illumina platform for four single nucleotide polymorphisms of ATM (rs189037, rs373759, and rs4585) and TP53 (rs1042522). The cumulative lens dose received during the entire life was estimated based on annual indoor and outdoor radiation doses and gender- and age-specific occupancy factors. Non-conditional logistic regression was performed to calculate odds ratio (OR) and 95% confidence intervals (95% CI).Results:ATM rs189037 and TP53 rs1042522 were significantly related to cortical and PSC opacity. The risk of opacity was higher when individuals carried the A allele of ATM rs189037 and C allele of TP53 rs1042522, compared with GG genotype. ATM rs189037 A allele carriers (AG/AA) and TP53 rs1042522 C allele carriers (CG/CC) combined with a cumulative lens dose of 100 mGy or higher showed statistically significant opacity risks (OR = 5.51, 95% CI: 1.47-20.66; OR = 2.69, 95% CI: 1.10-6.60).Conclusion: The A allele of ATM rs189037 and C allele of TP53 rs1042522 increased the risk of lens opacity induced by radiation. These polymorphisms in ATM and TP53 might modify the risk of cortical and PSC opacity induced by chronic and prolonged low-dose radiation.

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The activity concentrations of 40K, 210Pb, 210Po, 226Ra, 228Ra, 228Th, 230Th, 232Th, 234U, and 238U were determined in 82 food samples, grouped into 20 food groups according to the Brazilian Total Diet, which reflects the dietary habits of a population, for the rural and urban areas of Poços de Caldas city, a High Background Radiation Area. The highest activity concentration found in the food samples was due to 40K being present in all types of food. Among the other radionuclides, high activity concentrations were found for 210Pb in beans and salt, 210Po in fish, 226Ra and 228Ra in nuts and seeds. The main food groups that contributed most to the effective dose, in urban and rural regions, were beans and beverages. The effective doses, due to the ingestion of the analysed food groups, were of 0.44 and 0.60 mSv y-1 and the lifetime cancer risks were 1.6 × 10-3 and 2.3 × 10-3 for the urban and rural Poços de Caldas population, respectively.

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PURPOSE: Long-term exposure to low dose radiation may trigger immune response and stimulate hormesis. Interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) play a crucial role in immune function. We aimed to explore the possible association of IL-2 and IL-2R gene polymorphisms with low dose radiation exposure, as well as the relationship with IL-2 gene expression in people residing in areas with a high background radiation in Yangjiang, China. MATERIALS AND METHODS: We recruited and assigned 54 native men residing in Yangxi County, Yangjiang city to the high natural background radiation (HNBR) group, and 53 native men residing in Hengpi County, Enping city to the control area (CA) group. All the participants wore a thermoluminescent dosimeter (TLD) for 90 days, and answered questionnaires. The serum levels of IL2, IL4, IL5, sIL2R, and tumor growth factor (TGF), and expression levels of IL2RA, IL2RB, IL2RG, and IL2 were also analyzed. Additionally, we tested 10 polymorphic loci associated with the IL-2 gene. RESULTS: The annual effective radiation doses in the HNBR and CA groups were 6.24 mSv y-1 and 1.95 mSv y-1, respectively. After adjusting for potential confounding factors, the serum levels of IL-2 and IL-5 were higher in the HNBR group than the CA group (p < .05), while the serum level of TGFß was lower in the HNBR group (p < .05). The IL-2 gene mRNA expression level was higher in the HNBR group than the CA group (p < .05). The IL-2RB rs76206423 AA allele showed significant variations in the HNBR group (p = .0381). CONCLUSIONS: Long-term exposure to low dose radiation may enhance immune function, and IL-2RB rs76206423 may be related to the expression of IL-2 by other coding variants. Moreover, our data provide a better understanding of the molecular mechanism of the immune response to low dose radiation.

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Man has been exposed to different levels of natural background radiation since the creation of human life. There are inhabited areas around the world with extraordinary levels of natural background radiation. The level of natural radiation in these areas is up to two orders of magnitude higher than other places. Areas such as Yangjiang, China; Guarapari, Brazil; and Kerala, India are among the areas with high levels of natural radiation. Ramsar a coastal city in North Iran has some inhabited areas with the highest known levels of background radiation around the world. People who live in high background radiation areas (HBRAs) such as Ramsar do not record any detrimental biological effects. While some cytogenetic studies conducted in HBRAs have shown increased frequencies of unstable chromosome aberration, other investigations failed to find a significant difference. This short review is an attempt to verify if induction of chromosomal anomalies in the lymphocytes of the residents of high background radiation areas is associated with increased cancer risk.

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Previous studies evidenced the critical role of the mismatch repair system in DNA damage recognition, cell cycle arrest, apoptosis and DNA repair. MLH1 and MSH2 genes belong to repairing complexes of mismatch repair system. The side effects of ionizing radiation on the human health were proved, but researches on the inhabitants of high background radiation areas, with extra-ordinary radiation exposure, showed that the prevalence of cancer or radiation-related diseases is not significantly higher than normal background areas. The city of Ramsar, in northern Iran, has the highest level of natural background radiation in the world and in this study, we aimed to evaluate the expression of MLH1 and MSH2 genes among the inhabitants of high background radiation areas of Ramsar compared to normal background radiation areas. In the present study, 60 blood sample from high and normal background inhabitants were collected and we MLH1, and MSH2 genes expressions in residents of high background radiation area compared with normal background radiation area were evaluated by Quantitative Real-Time PCR. Our results showed a significant upregulation of MLH1 in residents of high background radiation area. Also, there is a significant association between MLH1 and MSH2 gene expression in both sexes. Also, the increased expression of MLH1 in HBRA is notable. There is an increased expression of MLH1 in age above 50 and a decreased expression of MSH2 in ages under 50 years (P < 0.0001). These findings are suggesting the triggering of Mismatch Repair system in response to high-level of natural background radiation.

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Biomass-based decontamination methods are among the most interesting water treatment techniques. In this study, 2 cyanobacterial strains, Nostoc punctiforme A.S/S4 and Chroococcidiopsis thermalis S.M/S9, isolated from hot springs containing high concentrations of radium (226Ra), were studied to be associated with removal of radionuclides (238U and 226Ra) and heavy metal cadmium (Cd) from aqueous solutions. The adsorption equilibrium data was described by Langmuir and Freundlich isotherm models. Kinetic studies indicated that the sorption of 3 metals followed pseudo-second-order kinetics. Effects of biomass concentration, pH, contact time, and initial metal concentration on adsorption were also investigated. Fourier-transform infrared spectroscopy revealed active binding sites on the cyanobacterial biomass. The obtained maximum biosorption capacities were 630 mg g-1 and 37 kBq g-1 for 238U and 226Ra for N. punctiforme and 730 mg g-1 and 55 kBq g-1 for C. thermalis. These 2 strains showed maximum binding capacity 160 and 225 mg g-1, respectively for Cd adsorption. These results suggest that radioactivity resistant cyanobacteria could be employed as an efficient adsorbent for decontamination of multi-component, radioactive and industrial wastewater.

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Naturally occurring radiation can be found all around us and account for most of the radiation received by human beings each year. Indonesia has a region with high-dose natural radiation located in the suburb of West Sulawesi province with a dose rate up to 2800 nSv/h; however, its impact was not fully understood. The aim of this study was to evaluate the radiosensitivity of 12 peripheral blood lymphocytes of inhabitant from high background radiation area (HBRA) and 10 from normal background radiation area (NBRA) based on cytokinesis-block micronucleus (CBMN) assay after challenged with 1.5 Gy of gamma ray. The analysis of CBMN was done according to standard procedure as per IAEA guidelines, and frequency of binucleate (mitotic) cells with micronuclei (MN) was scored in around 2000 binucleate lymphocytes cells per culture in microscopic analysis. Mean MN frequency for HBRA was lower than that of NBRA (0.121 vs. 0.189) after irradiation, indicating an adaptive response in HBRA group that resulted in less radiosensitivity; however, there was no statistically significant different (P > 0.05) between these two groups. The MN number was higher in women compared to men for both HBRA (0.15 vs. 0.09) and NBRA (0.216 vs. 0.147) groups. Besides, there was no statistically significant difference (P > 0.05) in Nuclear Division Index (NDI), as measured in 500 metaphase cells with published formula, between HBRA and NBRA samples (1.24 vs. 1.21). The lower MN frequency prompts us to conclude that there is an adaptive response in the lymphocytes of inhabitants as an indicator of lower radiosensitivity to the high natural radiation exposure. Further studies using large number of samples are required to obtain more comprehensive conclusion along with the assessment of other types of radiosensitivity-related biomarkers.

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This paper presents the radiometric survey results of the Mrima-Kiruku high background radiation (HBR) anomaly complex of south coastal Kenya. Utilizing a portable γ-ray spectrometer consisting of a 2.0 l NaI(Tl) backpack detector integrated with GPS to perform the relevant in-situ radiometric measurements, a novel geospatial gating method was devised to represent the measurements. The goal of this study was to assess radiation exposure and associated natural radioactivity levels in the complex and to compare the results obtained with those from previous preliminary related studies. Absorbed dose-rates in air were found to range <60-2368 nGy h-1. These rates were observed to correspond with the spatial variability of the underlying geology and terrain, increasing toward the summits of both Mrima and Kiruku Hills which implies that the complex is a geogenic HBR anomaly. The activity concentrations of 232Th in the study area are generally higher than those of 40K and 238U: The means of 40K, 238U and 232Th ranged 235±19-603±28 Bq kg-1, 68±6-326±24 Bq kg-1 and 386±12-1817±51 Bq kg-1 respectively. It was concluded that the high air absorbed dose-rate values that were measured (>600 nGy h-1) are due to elevated activity concentrations of 232Th. Therefore there is significant (>1 mSv/y) radiological hazard to the inhabitants of the area particularly those who reside at the foothills of both Mrima and Kiruku Hills.

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High expression of phospho histone γ-H2AX, a sensitive marker of double stranded DNA damage, is believed to be an indication of defective DNA repair pathway or genomic instability that may cause mutations and ultimately cancer. DNA damage can be caused by ionizing radiation exposure. Beside in medical treatment/diagnosis or industry, ionizing radiation exposure can also be found in naturally in regions of high natural back ground radiation. In this study we collect the blood from 45 volunteers living in Mamuju, a region with highest natural radiation in Indonesia (dose of ∼7 mSv/year). Subjects were grouped as high natural background area (HNBA) (n = 37) and control area (n = 8). The expression γ-H2AX foci were evaluated by one of researcher fluorescence microscope examination. Our results show that the average foci numbers per cell were in the normal range. While not statistical different, the average of γ-H2AX foci in exposed area higher in the exposed compared to the control area, 0.31 versus 0.13 (p > 0.05), respectively. Moreover, there was also no statistical difference of average γ-H2AX foci between man and woman, old and young people in exposed and control area (p > 0.05). In this preliminary study we find that γ-H2AX foci (and thus DNA double strand break) frequency in residents living in the HNBA of Mamuju, West Sulawesi, show a trend towards higher (albeit not significant) average values relative to the control area. More research is needed to further scrutinize these observations.

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Objective To explore the effect of long-term low dose ionizing radiation on telomere length in adults. Methods Forty female residents aged more than 55 years old from high level natural background radiation area in Yangjiang city and forty age-matched female residents from control area in Enping city were selected by quota sampling as high background group and control group, respectively. Genomic DNA was isolated from their peripheral blood. Telomere length was determined using real time q-PCR. The t-test was used to compare the square roots of the means of two groups. The individuals were divided into four groups based on ages ( 55 -, 60 -, 65 - and ≥70 ) and four groups based on BMI ( <18. 5, 18. 5-23. 99, 24. 0 -27. 99 and ≥28. 0). After adjusting age and BMI, multivariate linear regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. The individuals were divided into longer telomere length group (≥2 ) and shorter telomere length group ( <2). Logistic regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. Results The average cumulative dose was(169. 52 ± 27. 43)mSv for high background group and(47. 52 ± 6. 50)mSv for control group. The telomere length of high background group was( 1. 98 ± 1. 25 ) , shorter than that of control group ( 2. 69 ± 1. 44 ) with statis-tically significant difference(t=2. 24, P <0. 05). The multivariate linear regression analysis revealed that the effect of cumulative dose on telomere length was not significant ( P>0. 05 ) . Association between telomere length and cumulative dose was explored through Logistic regression, and odds ratio was taken as 0. 992(95% CI, 0. 985-0. 999 ) . There was a weak inverse association between telomere length and cumulative dose, because the odds ratio ( OR) was very close to 1. Conclusions No obvious dose-effect relationship between telomere length of residents and cumulative radiation doses was found. But the long-term low dose ionizing radiation may lead to the shortening of the telomere length in adults.

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The Chhatrapur placer deposit is found in a high background radiation area which has been recently identified on the southeastern coast of India. Previously, some geochemical studies of this area were carried out to assess external dose from radionuclides-bearing heavy mineral sands. In this study, radon, thoron and thoron progeny concentrations were measured in about 100 dwellings during three seasons (autumn-winter, summer, and rainy) in a 10- to 12-month period and annual doses due to inhalation of them were evaluated. The measurements were made by passive-type radon-thoron discriminative detectors and thoron progeny detectors in which solid state nuclear track detectors were deployed. The results show that radon and thoron concentrations differ by one order of magnitude depending on exposure periods, while thoron progeny concentration is nearly constant throughout the year. Since thorium-rich sand is distributed in the studied area, exposure to thoron is equal to, or exceeds, exposure to radon and is not negligible for dose evaluation. Based on the measurements, doses due to inhalation of radon and thoron are evaluated as 0.1-1.6 mSv y-1 and 0.2-3.8 mSv y-1, respectively. The total dose is 0.8-4.6 mSv y-1, which is the same order of magnitude as the worldwide value.

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Objective To increase the statistic power to estimate radiation-induced cancer risk on the basis of analysis of the 1999-2002 follow-up data from high background radiation areas (HBRA), in combination with those in the period 1979-1998, and further to estimate radiation-induced cancer risk at low dose after adjustment of individual smoking factor.Methods Cohort studies were conducted of cancer mortality for the residents in both HBRA and control area (CA), with follow-up made in phases.The present study was first focused on the collection of cancer mortality data during 1999-2002, with preliminary analysis of the risks of cancer mortality.And then, the effort was dedicated to analysis of both the risks of cancer mortality and the smoker-adjusted risks of radiation-induced cancer mortality from for the residents in HBRA in period 1999-2002 based on the pooled data during 1999-2002 and 1979-1998 through ID record linkage.Person-years were estimated using Epicure/DATAB model.The relative risk (RR), the excess relative risk coefficient (ERR/Sv) and confidence interval (CI) of cancer mortality from 1979 to 2002 were estimated using Poisson regress model in AMFIT mode.Results A total of 76 264 persons in HBRA and CA was followed up during 1999-2002, covering 300 523 person-years and 2 267 deaths identified, including 239 cancer deaths.Based on pooled data, 125 079 persons were followed up during 1979-2002, which covered 2 293 463 person-years and 14 711 deaths identified, including 1 441 died of cancer.The sex-and age-adjusted RR of all cancers in the HBRA during 1979-2002 was 0.99 (95％ CI: 0.89 to 1.11), showing no statistically significant differences between HBRA and CA (P ＞ 0.05).The value of ERR/Sv of all cancer mortality during 1979-2002 was-0.01 (95％ CI:-0.50 to 0.64).Smoker-adjusted RR of all cancer mortality in HBRA during 1987-2002 was 1.00 (95％ CI:0.87 to 1.15), with no statistically significant difference (P ＞ 0.05).The value of ERR/Sv for all cancers during 1987-2002 was 0.01 (95％ CI:-0.56 to 0.81) after adjustment of smoking.Conclusions Increased risk was not found in relation to radiation exposure at low dose in HBRA.After adjustment of smoking, the statistical difference has not been shown in all cancer mortality between HBRA and CA, but excess relative risk increased slightly.

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In India, High Background Radiation Areas (HBRAs) due to enhanced levels of naturally occurring radionuclides in soil (thorium and, to a lesser extent, uranium), are located along some parts of the coastal tracts viz. the coastal belt of Kerala, Tamilnadu and Odisha. It is conjectured that these deposits will result in higher emissions of radon isotopes ((222)Rn and (220)Rn) and their daughter products as compared to Normal Background Radiation Areas (NBRAs). While the annual external dose rates contributed by gamma radiations in these areas are about 5-10 times higher, the extent of increase in the inhalation dose rates attributable to (222)Rn and (220)Rn and their decay products is not well quantified. Towards this, systematic indoor surveys were conducted wherein simultaneous measurements of time integrated (222)Rn and (220)Rn gas and their decay product concentrations was carried out in around 800 houses in the HBRAs of Kerala and Odisha to estimate the inhalation doses. All gas measurements were carried out using pin-hole cup dosimeters while the progeny measurements were with samplers and systems based on the Direct radon/thoron Progeny sensors (DRPS/DTPS). To corroborate these passive measurements of decay products concentrations, active sampling was also carried out in a few houses. The results of the surveys provide a strong evidence to conclude that the inhalation doses due to (222)Rn and (220)Rn gas and their decay products in these HBRAs are in the same range as observed in the NBRAs in India.

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In the current study, different protein expression profiles in a strain Brevundimonas sp. ZF12, isolated from the aqueous zone containing high levels of radiation, were characterized following exposure to cadmium (II) using a proteomic strategy. In order to gain a deeper understanding of the cellular events that allow this strain to survive and undergo cadmium adaptation and sorption, the strain was tested under three experimental conditions of 5, 10 and 30 ppm cadmium (II) ions stress. Two-dimensional polyacrylamide gel electrophoresis and mass spectrometry were used to identify the differentially expressed proteins under cadmium (II) stress. 20 differentially expressed spots were successfully identified by MS/MS analysis. These proteins are involved in DNA repair and protection, amino acid metabolism, nucleotide metabolism, energy homeostasis, oxidative stress response, redox homeostasis, protein folding and heat-shock response. The results obviously indicate that the ZF12 strain tends to endure the cadmium (II) stress conditions by modification in many aspects of its cellular physiology and metabolism.

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PURPOSE: The effective dose received by humans from natural sources is about 2.4 mSv y(-1), but this is 10.2 mSv y(-1) for inhabitants of Ramsar, a city in northern Iran. Carcinogenesis is one of the most studied effects of radiation, especially in high doses. Nonetheless carcinogenesis of low doses is uncertain. A recent epidemiological study in high background radiation areas of Ramsar showed that the cancer incidence in this era is lower than neighbors. The reason of this different behavior is under study yet. NK cells, helper, and Cytotoxic T cells are most important components of the tumor immune surveillance. The counts and activities of these cells and also leukocytes, lymphocyte, neutrophil cells, and other important parameters were studied in the residents of Ramsar with different duration of exposure to chronic low dose radiation. MATERIALS AND METHODS: Fifty residents of high background radiation areas, who were between 25 and 35 years and fully healthy, were selected randomly and their consent was obtained. Then, 2 cc fresh peripheral bloods were taken in sterile conditions. Complete blood cell counts were performed by an automatic hematology analyzer and CD4+, CD8+, NK, and CD107a+ cell counts were determined by monoclonal antibodies and flowcytometry. CD4+ and CD8+ percentages and the CD4/CD8 ratio were determined and the data were analyzed using SPSS 16. RESULTS: The percentages of CD4+ cells increase, but the counts of CD107a+ cells decline in higher exposure durations. The other parameters did not have significant regression with exposure duration. CONCLUSIONS: These confirm that living in high background radiation areas may induce changes in the immune system gradually and address more investigations.

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The effective radiation dose of human from natural sources is about 2.4 mSv/y and the dose limit for radiation workers is 20 mSv/y. Ramsar, a city in Iran, has been the subject of concern in the last forty years for a high level of radiation measured in some spots as high as 260 mSv/y. Carcinogenesis is one of the most studied effects of radiation especially in high doses. Recent studies showed that the high level of natural radiation received by inhabitants of this area, paradoxically don't have significant health effect. Natural killer (NK) cells and cytotoxic T cells are the most important cells in tumor immune surveillance and CD107a is a widely expressed intracellular protein located in the lysosomal/endosomal membrane. CD107a transiently located on the cell membrane can be used as a marker of CD8 + T cell degranulation following stimulation. It is also expressed, to a lower extent, on activated NK cells. In this study, 60 healthy people were selected randomly and their consent obtained and confounding factors such as sex, age, life-styles was matched then the count of activated NK and CD8 + cells was compared in high and normal background radiation areas inhabitants of Ramsar. After filling the questionnaire and measurement of background radiation, blood samples of 30 healthy people from each region were analyzed immediately by means of flowcytometry. The leukocytes and their subsets were not significantly different between two groups and the count of active cells was higher in control group. The result shows that the changes in immune system occur due to radiation and maybe it is as a result of higher radiosensitivity of activated cells.