ABSTRACT
Individual doses from external γ-rays were estimated using biological dosimetry based on limited samplings (n1= 15 and n2 12 individuals) which comprised the Mayak workers group with acute radiation sickness (ARS). The following primary data were used for calculation as initial parameters: estimated dose from ex- ternal γ-rays based on physical dosimetry methods - D (Gy); time before first vomiting - T (h); number of lymphocytes in peripheral blood on a second day after acute radiation exposure - L (109/1); number of neutrophils in blood during first hours after accidental radiation exposure - N(109/). A number of mathe- matical models used for dose estimation were verified: power-law dependence of the absorbed dose from ex- ternal γ-rays (D) on time before first vomiting (7), exponential dependence of D on the number of lympho- cytes in peripheral blood (L), dependence of D on the number of neutrophils in peripheral blood (N) and complex models forD association with Tand L parameters as well as-with Tand Nparameters. The biological dosimetry technique based on a complex approach was shown to provide the best agreement with physical dosimetry methods for individual assessment of doses from external γ-rays.
Subject(s)
Radiation Dosage , Radiation Exposure/standards , Radiation Injuries/diagnosis , Radiometry/methods , Dose-Response Relationship, Radiation , Female , Gamma Rays/adverse effects , Humans , Lymphocytes/pathology , Lymphocytes/radiation effects , Male , Occupational Exposure , Radiation Injuries/blood , Radiation Injuries/etiology , Radiation Injuries/pathology , Radiometry/standardsABSTRACT
An association between polymorphic variants of key genes of base excision repair (BER) and lung cancer was studied in "Mayak" workers occupationally exposed to prolonged external y-rays and internal α-radiation from incorporated (239)Pu. The study was "case-control". The group of "cases" consists of 75 "Mayak" workers with the verified diagnosis of "lung cancer". At the moment of diagnosis the mean total absorbed dose from external y-rays to whole body was 1.19 Gy; the mean total absorbed dose from internal α-radiation due to incorporated (239)Pu in lung was 0.31 Gy. The group of "controls" includes "Mayak" workers matched by sex and birth year without lung cancer and other cancers during the study period (141 individuals). Increased lung cancer risk was revealed in workers-carriers of homozygous minor genotype of genes OGG] Ser326Cys (OR - 4.67, p = 0.007), APEI Asp148Glu (OR = 1.82, p = 0.063) and XRCC1 Gln399Arg (OR = 2.86, p = 0.026). Increased lung cancer risk was revealed in carriers of different pairwise combinations of minor genotypes of the studied genes of BER or in carriers of pairwise combinations with one homozygous minor mm-genotype and the other homozygous major ww genotype. Thus, OR of lung cancer in carriers of pairwise genotypes of mm genes OGG] Ser326Cys and APE] Asp 148Glu was 12.17.
Subject(s)
DNA Glycosylases/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Lung Neoplasms/genetics , Neoplasms, Radiation-Induced/genetics , X-ray Repair Cross Complementing Protein 1/genetics , Adult , Aged , Alpha Particles/adverse effects , DNA Repair/genetics , DNA Repair/radiation effects , Female , Gamma Rays/adverse effects , Genetic Predisposition to Disease , Genotype , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Male , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Occupational ExposureABSTRACT
OBJECTIVE: to assess mutational events in exons 5, 7, and 8 of the p53 gene and to reveal mutant p53 protein in verified cases of morphologically altered (proliferative and precancerous changes, lung cancer) and histologically unaltered, lung tissues in workers exposed to occupational radiation. MATERIAL AND METHODS: The investigation used formalin-fixed paraffin-embedded unaltered and altered lung tissue blocks (FFPBs) obtained from the human radiobiological tissue repository. The shelf-life of FFPBs was 5-31 years. An immunohistochemical technique using mouse antibodies against p53 protein (<
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Neoplasms, Radiation-Induced/pathology , Nuclear Energy , Occupational Diseases/pathology , Precancerous Conditions/pathology , Tumor Suppressor Protein p53/genetics , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis , DNA, Neoplasm/genetics , Exons , Humans , Immunohistochemistry , Industry , Lung/metabolism , Lung/pathology , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Mutation , Neoplasm Staging , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/genetics , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Occupational Diseases/genetics , Occupational Exposure/adverse effects , Occupational Exposure/analysis , Paraffin Embedding , Precancerous Conditions/epidemiology , Precancerous Conditions/etiology , Precancerous Conditions/genetics , RussiaABSTRACT
Genome instability transmission in offspring was analyzed in order to evaluate the risk of delayed genetic effects of exposure in 95 family triplets in which only fathers experienced prolonged occupational radiation exposure. The mean total preconceptive absorbed dose (TPAD) of external gamma radiation in the paternal gonads was 1.65 ± 0.08 Gy (dose range of 0.57-5.70 Gy), and the mean TPAD of internal alpha radiation from incorporated plutonium-239 in.the gonads was 0.0015 ± 0.0003 Gy (dose range 0.000-0.015 Gy). The control group consisted of 50 family triplets in which parents were not occupationally exposed. The mutation process was studied using PCR based on hypervariable minisatellite marker CEB 1 (chromosome 2, 2q37.3). The paternal type of inheritance of mutations for minisatellite CEB 1 was found in 80% of cases. The analysis revealed a statistically significant increase in minisatellite CEB1 mutations in the common group of families in which fathers experienced prolonged occupational radiation exposure and in the group of families in which fathers were exposed to radiation in a dosage range of 0.5-1.0 Gy as compared to the control, reaching a significance level of p = 0.109 and p = 0.058, respectively. The dose threshold of mutation detection in the off-spring of Mayak PA workers was estimated.
Subject(s)
Alpha Particles/adverse effects , Gamma Rays/adverse effects , Genomic Instability/genetics , Maternal Exposure/adverse effects , Minisatellite Repeats , Occupational Exposure/adverse effects , Paternal Exposure/adverse effects , Radiation Injuries/genetics , Chromosomes, Human, Pair 2/genetics , Family , Female , Genomic Instability/radiation effects , Humans , Male , MutationABSTRACT
An association between polymorphous (allelic) gene variants of phase II of enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione-S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers exposed occupationally to prolonged external γ-rays and internal α-radiation from incorporated 239Pu was studied. Analysis of the population frequency of genotypes and alleles of the studied genes in the cohort of Mayak workers revealed their compliance with the Hardy-Weinberg principle and with the corresponding frequency in the European population. The study was based on the case-control method. A case-group consisted of 49 Mayal workers with a verified diagnosis of lung cancer. The mean total absorbed dose from external γ-rays at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from internal α-radiation from incorporated 239Pu to lung was 0.35 Gy. Control consisted of 172 Mayak workers matched by the year of birth, gender, and age at the moment of employment at one of the main facilities with no lung cancer registered within the study period. No increase in the relative risk of lung cancer (odds ratio, OR) was revealed among the individuals with deletion variants of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as compared to the individuals with ww or wp genotype, which was determined in total for these genes (normal or partly decreased gene activity). An increase in OR of lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found in the carriers with a complete absence of the product of genes GSTP1*B and NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant decrease in OR of lung cancer was found in the wp genotype carriers of gene GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene alleles were established in the carriers with a statistically significant increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6 590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp GSTT1*0).
Subject(s)
Arylamine N-Acetyltransferase/genetics , Glutathione S-Transferase pi/genetics , Glutathione Transferase/genetics , Lung Neoplasms/genetics , Neoplasms, Radiation-Induced/genetics , Occupational Diseases/genetics , Polymorphism, Single Nucleotide , Radiation, Ionizing , Xenobiotics/pharmacokinetics , Aged , Alpha Particles/adverse effects , Case-Control Studies , Female , Gamma Rays/adverse effects , Genetic Predisposition to Disease , Genotype , Humans , Industry , Lung Neoplasms/enzymology , Lung Neoplasms/metabolism , Male , Metabolic Detoxication, Phase II , Neoplasms, Radiation-Induced/enzymology , Neoplasms, Radiation-Induced/metabolism , Occupational Diseases/enzymology , Occupational Diseases/metabolism , Occupational Exposure/adverse effects , Polymorphism, Restriction Fragment Length , RussiaABSTRACT
Mathematical methods were developed to construct dose and time distributions and their associated risks and threshold values for lethal and non-lethal effects of acute radiation exposure to include mortality and incidence, prodromal vomiting, and agranulocytosis. A new distribution (T-model) was obtained to describe time parameters of acute radiation syndrome such as the latency period, time to onset of vomiting, and time to initiation of agranulocytosis. Based on the dose and time distributions, the parameter translation method was defined using an orthogonal regression, which allows one to solve for these distributions in the case of acute radiation exposure. The assessment of threshold doses was performed for some effects of acute radiation syndrome: for the latency period, â¼6-8 Gy absorbed dose and â¼0.7-0.9 h time to onset of vomiting; and for incidence (agranulocytosis), â¼2-3 Gy absorbed dose and â¼2-3 h time to onset of vomiting. The obtained new formula for assessment of radiation risk is applicable to the time parameters of acute radiation syndrome.
Subject(s)
Acute Radiation Syndrome/etiology , Radiation Dosage , Dose-Response Relationship, Radiation , Humans , Regression Analysis , Time FactorsABSTRACT
The research objective is assessment of structural genomic damages in plutonium workers. The study group included the Mayak nuclear workers subject to chronic occupational exposure to incorporated 239Pu and/or external gamma-rays. The analysis was performed based on the culture of lymphocytes in peripheral blood. The yield of intra-chromosomal exchange aberrations of chromosomal type on stained slides was analyzed using in situ fluorescent hybridization, mBAND. Linear relationships were revealed between (a) the total yield of chromosomal type aberrations (e.g. intra- and inter-chromosomal ones) and an absorbed dose from external exposure of the red bone marrow to gamma-rays, an absorbed dose from internal exposure to a-radiation from incorporated 239Pu; and (b) the yield of intra-chromosomal exchange aberrations of chromosomal type and an absorbed dose from exposure of the red bone marrow to 239Pu and 239Pu body burden.
Subject(s)
Chromosome Aberrations/radiation effects , Gamma Rays , Genome, Human/radiation effects , Nuclear Reactors , Occupational Exposure/adverse effects , Plutonium , Aged , Body Burden , Chromosome Aberrations/statistics & numerical data , Cytogenetic Analysis , Dose-Response Relationship, Radiation , Female , Humans , Least-Squares Analysis , Linear Models , Lymphocytes/radiation effects , Male , Plutonium/blood , RussiaABSTRACT
Analysis of chronic morbidity parameters in workers engaged into processing and utilization of arms and military equipment did not reveal any case of occupational radiation disease over 30 years of medical observation. Standardized parameters in general and in separate diseases classes did not differ with general data collected in Russia. Occurrence of separate entities did not depend on influence of radiation factors.
Subject(s)
Industry/instrumentation , Military Personnel , Occupational Diseases/epidemiology , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Morbidity/trends , Russia/epidemiologyABSTRACT
The genome status in somatic cells was assessed using the chromosomal aberration (CA) test in peripheral blood lymphocytes from 194 plutonium workers exposed to occupational radiation mainly from low-transportable compounds of airborne 230Pu. Pu body burden at the time of cytogenetic study varied from values close to the method sensitivity to values multiply exceeding the permissible level. Standard (routine) methods of peripheral blood lymphocytes cultivation were applied. Chromatid- and chromosomal-type structural changes were estimated. Aberrations were estimated per 100 examined metaphase cells. The quantitative relationship between the CA frequency and Pu body burden and the absorbed dose to the lung was found. Mathematical processing of results was carried out based on the phenomenological model. The results were shown as theoretical and experimental curves. The threshold of the CA yield was 0.43 +/- 0.03 kBq (Pu body burden) and 6.12 +/- 1.20 cGy (absorbed dose to the lung).
Subject(s)
Chromosome Aberrations , Lymphocytes/radiation effects , Occupational Exposure/adverse effects , Plutonium/adverse effects , Adult , Aerosols , Aged , Body Burden , Cells, Cultured , Dose-Response Relationship, Radiation , Gamma Rays/adverse effects , Humans , Lung/radiation effects , Middle Aged , Models, GeneticABSTRACT
Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathematical model that was introduced for simultaneous assessment of radiation and cigarette-smoking-related damage to the respiratory system. The model incorporates absolute thresholds for smoking- and radiation-induced respiratory system dysfunction. As the alpha radiation dose to the lung increased from 0 to 4.36 Gy, respiratory function indices studied decreased, although remaining in the normal range. The data were consistent with the view that alpha radiation doses to the lung above a relatively small threshold (0.15 to 0.39 Gy) cause some respiratory system dysfunction. Respiratory function indices were not found to be influenced by total-body gamma radiation doses in the range 0-3.8 Gy when delivered at low rates over years. However, significant decreases in airway conductance were found to be associated with cigarette smoking. Whether the indicated cigarette smoking and alpha radiation associated dysfunction is debilitating is unclear.
ABSTRACT
A DNA bank was created to preserve the genetic material of staff of the first Russian atomic plant, Production Association (PO) Mayak, who were exposed to chronic external gamma-irradiation at various doses in the early years of plant operation. Some of the workers experienced combined irradiation from external and internal (incorporated plutonium-239) sources. The unique genetic material of the subjects and their children can be used to study the remote consequences of irradiation by means of modern molecular-genetic techniques. At present, the bank contains the genetic material of 500 people. A database was constructed to include medical, demographic, professional, and dose characteristics of each individual and quantitative and qualitative parameters of each DNA preparation. The bank is continuously augmented with new DNA samples of the irradiated people and members of their families.
Subject(s)
DNA/radiation effects , Occupational Exposure , Humans , Radiation, Ionizing , Specimen HandlingABSTRACT
During a Phase-I effort, studies were planned to evaluate deterministic (nonstochastic) effects of chronic exposure of nuclear workers at the Mayak atomic complex in the former Soviet Union to relatively high levels (> 0.25 Gy) of ionizing radiation. The Mayak complex has been used, since the late 1940's, to produce plutonium for nuclear weapons. Workers at Site A of the complex were involved in plutonium breeding using nuclear reactors, and some were exposed to relatively large doses of gamma rays plus relatively small neutron doses. The Weibull normalized-dose model, which has been set up to evaluate the risk of specific deterministic effects of combined, continuous exposure of humans to alpha, beta, and gamma radiations, is here adapted for chronic exposure to gamma rays and neutrons during repeated 6-h work shifts--as occurred for some nuclear workers at Site A. Using the adapted model, key conclusions were reached that will facilitate a Phase-II study of deterministic effects among Mayak workers. These conclusions include the following: (1) neutron doses may be more important for Mayak workers than for Japanese A-bomb victims in Hiroshima and can be accounted for using an adjusted dose (which accounts for neutron relative biological effectiveness); (2) to account for dose-rate effects, normalized dose X (a dimensionless fraction of an LD50 or ED50) can be evaluated in terms of an adjusted dose; (3) nonlinear dose-response curves for the risk of death via the hematopoietic mode can be converted to linear dose-response curves (for low levels of risk) using a newly proposed dimensionless dose, D = X(V), in units of Oklad (where D is pronounced "deh"), and V is the shape parameter in the Weibull model; (4) for X < or = Xo, where Xo is the threshold normalized dose, D = 0; (5) unlike absorbed dose, the dose D can be averaged over different Mayak workers in order to calculate the average risk of death via the hematopoietic mode for the population exposed at Site A; and (6) the expected cases of death via the hematopoietic syndrome mode for Mayak workers chronically exposed during work shifts at Site A to gamma rays and neutrons can be predicted using ln(2)B M[D]; where B (pronounced "beh") is the number of workers at risk (criticality accident victims excluded); and M[D] is the average (mean) value of D (averaged over the worker population at risk, for Site A, for the time period considered). These results can be used to facilitate a Phase II study of deterministic radiation effects among Mayak workers chronically exposed to gamma rays and neutrons.