Cancer risks in a population with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings, 1983-2002.

PURPOSE: To assess cancer risks in a population that received prolonged low dose-rate gamma-irradiation for about 10 years as a result of occupying buildings containing 60Co-contaminated steel in Taiwan. MATERIALS AND METHODS: The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis. RESULT: A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range < 1 - 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 - 7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0 - 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age. CONCLUSIONS: The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.

Exposure temperature, but not donor age, is a confounding factor for in vitro translocation production by chronic irradiation.

PURPOSE: To assess the effects of incubation temperature during irradiation, and of donor age, on the in vitro induction of chromosomal translocations in human lymphocytes. MATERIAL AND METHODS: Lymphocytes from six human male donors were scored, using fluorescence in situ hybridization, for the presence of chromosomal translocations involving chromosomes 1 to 6 after in vitro, chronic exposure (delivered continuously over 48 h at 37 degrees C or at 20 degrees C) to tritium beta-rays or 60Co gamma-rays. RESULTS: No age-related difference in the alpha coefficients of the fitted induction curves was observed for gamma-ray-exposed lymphocytes obtained from four donors whose ages ranged from 24 to 79 years, or for tritium beta-ray-exposed lymphocytes from two donors aged 36 and 62 years. Duplicate samples from one donor, irradiated concurrently at 20 degrees C or 37 degrees C, gave significantly different alpha coefficients: 0.128+/-0.008 and 0.053+/-0.004, respectively (p<0.0001). The S-ratio (the ratio of induced complete to incomplete translocations) was found to be independent of radiation dose, donor age and exposure temperature. CONCLUSIONS: For biodosimetry in chronic irradiation situations, the use of alpha coefficients derived from the dose-response curves of cells chronically irradiated in vitro at body temperature is recommended. With respect to induction rates, donor age does not appear to be a confounding factor. The S-ratio is independent of radiation doses, exposure temperatures, or donor ages.

Biodosimetry using chromosomal translocations measured by FISH in a population chronically exposed to low dose-rate 60Co gamma-irradiation.

PURPOSE: To evaluate the cumulative gamma-radiation personal exposure by analysing lymphocyte chromosome translocations using FISH painting and to compare FISH-derived biodoses with those derived from retrospective physical dose reconstruction in residents receiving chronic low dose-rate gamma-irradiation while living in radio-contaminated buildings. MATERIALS AND METHODS: Chromosome translocation frequencies were evaluated by scoring 933 to 3077 metaphases under fluorescence microscope for each of the five male and four female exposed individuals after they had relocated from the radioactive environment for 34-82 months. FISH painting was conducted using kits of whole-chromosome probes for chromosomes 1, 2 and 4 in orange and 3, 5 and 6 in green and counter-stained with 4',6-diamidino-2-phenylindole (DAPI). The retrospective dose estimation termed Taiwan Cumulative Dose (TCD) was conducted by assessment using detailed information of historical exposure and the environmental radioactivity for each apartment during previous residency. RESULTS: A total of 20 244 well-prepared metaphases were scored. Biodoses were calculated from the translocation frequencies and physical doses were estimated from detail questionnaires for each individual. The translocation frequencies measured ranged from 2.2x10(-3) to 26.8x10(-3) translocations per cell and the dose equivalent from 52.2 to 992.2mSv. A good correlation was observed between the physical and biodoses. A plot of TCD against FISH-derived doses produced D(fish) =0.65 D(TCD), when fitted by a linear model, and D(fish) = 0.53 D(TCD)+ 1.26x10(-4 ) D(2)(TCD), when fitted with a linear-quadratic model. Given the scatter in the data and the extremely small quadratic dose contribution, neither model could be ruled out. CONCLUSION: Chromosome translocations provide a valid method of dose estimation in extremely protracted low dose-rate gamma-radiation exposure. Validation of the TCD method by FISH-measured translocations supports the use of TCD for epidemiological studies.

Alpha coefficient of dose-response for chromosome translocations measured by FISH in human lymphocytes exposed to chronic 60Co gamma rays at body temperature.

PURPOSE: To measure the alpha coefficient, the initial slope of the translocation dose-response curve, for 60Co gamma-rays in human lymphocytes. MATERIALS AND METHODS: Human lymphocytes were exposed to 0, 0.32, 0.62 and 0.92 Gy of chronic 60Co gamma-rays under conditions that reduce the metabolic stress to the cells. Chromosome translocation frequencies were measured using fluorescence in situ hybridization with a whole-chromosome probe cocktail specific for chromosomes 1, 2, 4 (orange) and 3, 5, 6 (green). RESULTS: A total of 72,383 metaphases were analysed (33,429 in exposed cells) in two individuals. The shape of the dose-response curves for translocations was linear, and alpha coefficient was measured as 0.024 +/- 0.002 translocations per cell per Gy for the combined data for two 24 year old male donors. CONCLUSION: The alpha coefficients measured after chronic exposure were in good agreement with that reported in the literature for acute, low-dose exposure of human lymphocytes to 60Co gamma-rays.

Follow-up in the micronucleus frequencies and its subsets in human population with chronic low-dose gamma-irradiation exposure.

Forty-eight individuals, who received protracted low-dose rate gamma-irradiation from radioactive environments for 2-10 years, have been evaluated repetitively for cytogenetic damage by the cytochalasin-B micronuclei assay (CBMN) after they relocated from radioactive buildings. These subjects were shown to have a significant decrease in the CBMN frequencies during 26.2+/-8.4 months of follow-up. By the mixed effect multiple linear regression analysis, the CBMN frequencies in these 48 subjects during repetitive measurements were significantly associated with the relocation duration since leaving the radioactive environments (relocation time or RT in months; estimate -0.47, standard error 0. 0016, p value 0.0074). The alteration rate in the proportions of binucleates carrying a single micronucleus and those with multiple micronuclei was further compared among 26 of these exposed individuals. The proportions of binucleates with multi-micronuclei were shown to decline significantly faster than those with a mono-micronucleus between these two repetitive assays (proportional Z-test, p value 0.003). Moreover, some of the exposed subjects were shown to have a persistent increase in the total micronuclei frequencies or carrying multi-micronuclei in the binuclei even 3-4 years post-cessation of exposure. This suggests potential genomic instability in stem cells of the exposed individuals and the phenomenon deserves further closer monitoring. Understanding the dynamics of micronucleus expression in lymphocytes in subjects with previous mutagenic exposure would be of significant importance for human population monitoring.

Dose estimation for repeated phosphorus-32 ingestion in human subjects.

Dose estimation was conducted for internal phosphorus-32 exposure in one young male subject from repeated oral mis-ingestion for > 1 year. Since disclosure for previous continuous contamination, a series of urine samples were collected from this individual weekly for a period of >2 months. P-32 radioactivity in urine samples were measured by the acid precipitation method. Estimation for retrospective total effective dose equivalent received by this subject was conducted for cumulative internal dose estimation. A minimum of 9.4 mSv was estimated for an assumed single ingestion. As this was a rare case in radiation protection and internal radiation dosimetry, its implications were of considerable significance.

Dynamics of changes in micronucleus frequencies in subjects post cessation of chronic low-dose radiation exposure.

To assess DNA damage remaining in peripheral lymphocytes, 48 individuals were evaluated twice for lymphocyte micronucleus frequencies by the cytokinesis-blocking cytochalasin B (CBMN) analysis post relocation from radio-contaminated apartments after various periods of time. The frequencies of CBMN at the first evaluation were significantly higher than those at the second examination (Chang et al., 1999c). These individuals were categorized into three groups: those with cumulative exposure of >300 mSv (defined as high exposure, HDose), those with 100-300 mSv (MDose) and those with <100 mSv (LDose). Using the Poisson mixed-effect model (Little et al., 1996), the estimated mean CBMN frequencies ( per thousand) for individuals in HDose, MDose and LDose exposure categories when they had only recently relocated were 21.8, 17.6 and 15.4, respectively. The estimated mean duration post relocation for the CBMN frequencies of these individuals to reduce to 10.2, the second CBMN frequency, on average, was 47.5, 37.2 and 28.3 months in the three exposure groups, respectively. The rates of change in CBMN frequencies were shown to be significantly higher in the HDose group than in the MDose and LDose groups. The results suggested a characteristic dose-dependent decline in the CBMN frequencies in the exposed population post cessation of chronic low-dose ionizing radiation exposure.

Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure.

Acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including increased frequencies of micronuclei and chromosomal aberrations. However, the cytogenetic effects of chronic low dose radiation exposure in vivo needs further characterization. Sixteen subjects with chronic low dose rates of gamma-radiation exposure from 60Co-contaminated steel in radioactive buildings were compared with seven non-exposed reference subjects for micronucleus frequencies after they relocated. By in situ hybridization using a digoxigenin-labeled anti-alpha all human centromere probe, the exposed subjects were shown to have a significant increase in cytochalasin B-modulated micronucleus (CBMN) frequencies, as well as a significant increase in centromere-positive (C+) CBMN, centromere-negative (C-) CBMN, total C+signals, single C+ MN signals and multiple C+ signals/1000 binucleated cells (BN). However, decreases in the ratios C+MN/C- MN and C+MN/total CBMN (%) were also noted in the exposed subjects. By mixed effects analysis, considering individuals from the same families, the C- MN and single C+ MN/1000 BN were both positively and moderately associated with previous cumulative exposure. When the time period of relocation post-exposure (relocation time or RT) was considered, total C+MN and multiple C+MN/1000 BN were negatively and significantly associated with RT. Moreover, the C+MN, C- MN, C+MN/C- MN ratio and single C+MN/1000 BN were all negatively and moderately associated with RT, but not with exposure dose. This suggested that acentromeric and single or multiple centromeric CBMN cytogenetic damage seems to disappear differentially in human subjects post chronic low dose radiation exposure.