Memory CD4 T-cell subsets discriminated by CD43 expression level in A-bomb survivors

Purpose:?Our previous study showed that radiation exposure reduced the diversity of repertoires of memory thymus-derived cells (T cells) with cluster of differentiation (CD)- 4 among atomic-bomb (A-bomb) survivors. To evaluate the maintenance of T-cell memory within A-bomb survivors 60 years after radiation exposure, we examined functionally distinct memory CD4 T-cell subsets in the peripheral blood lymphocytes of the survivors.

Methods:?Three functionally different subsets of memory CD4 T cells were identified by differential CD43 expression levels and measured using flow cytometry. These subsets consist of functionally mature memory cells, cells weakly responsive to antigenic stimulation, and those cells functionally anergic and prone to spontaneous apoptosis.

Results:?The percentages of these subsets within the peripheral blood CD4 T-cell pool all significantly increased with age. Percentages of functionally weak and anergic subsets were also found to increase with radiation dose, fitting to a log linear model. Within the memory CD4 T-cell pool, however, there was an inverse association between radiation dose and the percentage of functionally mature memory cells.

Conclusion:?These results suggest that the steady state of T cell memory, which is regulated by cell activation and/or cell survival processes in subsets, may have been perturbed by prior radiation exposure among A-bomb survivors.     

Lack of association between acute exposure to ionizing radiation and liver cirrhosis

PURPOSE: Although previous studies have shown significantly increased risks of liver cirrhosis and chronic liver disease for acute radiation exposure among survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, these studies have not taken into account hepatitis B virus (HBV) infections. Because HBV is associated with both A-bomb radiation and liver cirrhosis, our goal was to investigate the relationship of acute ionizing radiation to liver cirrhosis adjusting for HBV, co-occurring primary liver cancer (PLC), and other potential confounders. MATERIALS AND METHODS: Using a cross-sectional design and pathology review of a cohort of Japanese atomic-bomb survivors, we found that 213 of 335 (63.6%) subjects with PLC and 55 of 776 (7.1%) subjects without PLC had cirrhosis. RESULTS: We found no association between acute exposure to A-bomb radiation and liver cirrhosis. The adjusted odds ratio of cirrhosis per Sv liver irradiation was 0.59 (95% confidence interval: 0.27 - 1.27). Cirrhosis risks for the highest tertile of radiation exposure (mean exposure 0.7 Sv) were also not elevated (0.8, 0.26 - 2.12 and 0.2, 0.03 - 0.98 among subjects with and without PLC. CONCLUSIONS: Acute exposure to liver irradiation does not increase risks of liver cirrhosis, regardless of PLC status.     

Lack of association between acute exposure to ionizing radiationand liver cirrhosis

Purpose: Although previous studies have shown significantly increased risks of liver cirrhosis and chronic liver disease for acute radiation exposure among survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, these studies have not taken into account hepatitis B virus (HBV) infections. Because HBV is associated with both A-bomb radiation and liver cirrhosis, our goal was to investigate the relationship of acute ionizing radiation to liver cirrhosis adjusting for HBV, co-occurring primary liver cancer (PLC), and other potential confounders.

Materials and methods: Using a cross-sectional design and pathology review of a cohort of Japanese atomic-bomb survivors, we found that 213 of 335 (63.6%) subjects with PLC and 55 of 776 (7.1%) subjects without PLC had cirrhosis.

Results: We found no association between acute exposure to A-bomb radiation and liver cirrhosis. The adjusted odds ratio of cirrhosis per Sv liver irradiation was 0.59 (95% confidence interval: 0.27 – 1.27). Cirrhosis risks for the highest tertile of radiation exposure (mean exposure 0.7 Sv) were also not elevated (0.8, 0.26 – 2.12 and 0.2, 0.03 – 0.98 among subjects with and without PLC.

Conclusions: Acute exposure to liver irradiation does not increase risks of liver cirrhosis, regardless of PLC status.     

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.     

Detecting the health risks of radiation.

Radiation can cause both non-stochastic (cell-killing) effects, leading to burns, epilation, immune system damage and lens opacities, and mutational or stochastic effects due to low dose damage to single cells. If the latter are followed by clone formation or fertilization, the mutants are not recognized by the immune system, and there is no competing cause of death, cancer or leukaemia can result. These effects did not become public knowledge until after the A-bombings of Hiroshima and Nagasaki. Subsequent analysis of the data on A-bomb survivors suggests, contrary to official views, that the immune system has a complex role in the aetiology of cancer and leukaemia, and that the A-bomb survivors were unusually resistant to the harmful effects of the bombings. These findings require the re-evaluation of the effects of low-level radiation, which has increased with the growth of the nuclear industry, both civil and military.     

Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors

Purpose : Genetic alterations, including microsatellite instability (MSI), are ultimate steps toward malignant process. To investigate MSI in A-bomb survivors, leukaemic cells were analysed from 13 acute myelocytic leukaemia patients with a history of radiation exposure and also in 12 de novo patients. Materials and methods : To assess the microsatellite changes, a fluorescent system in 10 loci (BAT40, D3S643, D5S107, IRF1, MYC, D9S171, WT1, TP53, DM, D17S855) was used. Results : MSI analysis revealed a high frequency of multiple microsatellite changes in the exposed patients (84.6%) compared with non-exposed patients (8.3%). There was a significant difference (p <0.001) between the two groups. Conclusions : These analyses clearly demonstrate that leukaemic cells from heavily exposed patients contain a number of genetic instabilities that may strongly influence the development of leukaemia among people exposed to the Hiroshima A-bomb radiation.     

Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors

PURPOSE: Genetic alterations, including microsatellite instability (MSI), are ultimate steps toward malignant process. To investigate MSI in A-bomb survivors, leukaemic cells were analysed from 13 acute myelocytic leukaemia patients with a history of radiation exposure and also in 12 de novo patients. MATERIALS AND METHODS: To assess the microsatellite changes, a fluorescent system in 10 loci (BAT40, D3S643, D5S107, IRF1, MYC, D9S171, WT1, TP53, DM, D17S855) was used. RESULTS: MSI analysis revealed a high frequency of multiple microsatellite changes in the exposed patients (84.6%) compared with non-exposed patients (8.3%). There was a significant difference (p < 0.001) between the two groups. CONCLUSIONS: These analyses clearly demonstrate that leukaemic cells from heavily exposed patients contain a number of genetic instabilities that may strongly influence the development of leukaemia among people exposed to the Hiroshima A-bomb radiation.     

Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors

PURPOSES: To compare the radiation-associated relative risks of cancer incidence and mortality in groups exposed to ionizing radiation in the course of treatment for a variety of malignant and non-malignant conditions with those in the Japanese A-bomb survivor cancer incidence and mortality data. MATERIALS AND METHODS: Comparison of the excess relative risk coefficients derived from published information for each study with the excess relative risk coefficient in comparable (age at exposure, time since exposure, sex) matched subsets of the Japanese A-bomb survivor cancer incidence and mortality data. RESULTS: Sixty-five studies of persons who have received appreciable doses of ionizing radiation in the course of treatment and for whom there is adequate ascertainment of cancer incidence or mortality are identified, from which 116 cancer-site-specific estimates of excess relative risk are derived. Relative risks tend to be lower in the medical series than in the Japanese A-bomb survivors. The most marked discrepancies between the relative risks in the medical series and in the A-bomb survivors are for leukaemia, where 12 of the 17 medical studies have significantly lower relative risks than those observed in the Japanese data. However, the ratio between the relative risks in the medical studies and in the Japanese data tends to diminish with increasing average or maximal therapy dose. This is observed for all cancer sites and is particularly marked for leukaemia. After taking account of cell sterilization and dose fractionation the apparent differences between the relative risks for leukaemia in the Japanese A-bomb survivors and in the medical series largely disappear. This suggests that cell sterilization largely accounts for the discrepancy between the relative risks in the Japanese data and the medical studies. Other factors, such as the differences in underlying cancer risks between the Japanese A-bomb survivors and the medical series, and dose-fractionation effects, may also contribute. CONCLUSIONS: The relative risks of cancer in studies of persons exposed to appreciable doses of ionizing radiation in the course of treatment for a variety of malignant and non-malignant conditions are generally less than those in comparable subsets of the Japanese A-bomb survivor cancer incidence and mortality data. Cell sterilization effects can largely explain the discrepancy between the Japanese and the medical series.     

Problems Inherent in the Assessment of Long-TermLow-Dose Radiation Carcinogenesis

Risk estimates derived from studies based on actual exposure to low dose radiation(LDR),I. E populations exposed to fallout,those living in the vicinity of nuclear reactors,scattered x- radiation. Nuclear industry and in utero exposure(1-8),vary from extrapolations coming from highdose studies. i. e A-bomb survivors and indi viduals exposed to therapeutic irradiation(9-12).     

Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model

PURPOSES: To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk. MATERIALS AND METHODS: Fitting two sorts of time- and age-adjusted relative risk models to a case-control dataset nested within the Colorado Plateau uranium miner cohort and to the Japanese atomic (A)-bomb survivor mortality data. RESULTS: If all A-bomb survivors are compared with the Colorado data, there are statistically significant (two-sided p < 0.05) differences between the two datasets in the pattern of the variation of relative risk with time after exposure, age at exposure and attained age. The excess relative risk decreases much faster with time, age at exposure and attained age in the Colorado uranium miners than in the Japanese A-bomb survivors. If only male A-bomb survivors are compared with the Colorado data, there are no longer statistically significant differences between the two datasets in the pattern of variation of relative risk with time after exposure, age at exposure or attained age. There are no statistically significant differences between the male and female A-bomb survivors in the speed of reduction of relative risk with time after exposure, age at exposure or attained age, although there are indications of rather faster reduction of relative risk with time and age among male survivors than among female survivors. The implicit risk conversion factor for exposure to radon progeny relative to the A-bomb radiation in the male survivors is 1.8 x 10(-2) Sv WLM(-1) (95% CI 6.1 x10(-3), 1.1 x 10(-1)) using a model with exponential adjustments for the effects of radiation for time since exposure and age at exposure, and 1.9 x 10(-2) Sv WLM(-1) (95% CI 6.2 x 10(-3), 1.6 x 10(-1)) using a model with adjustments for the effects of radiation proportional to powers of time since exposure and attained age. Estimates of the risk conversion factor calculated using variant assumptions as to the definition of lung cancer in the Colorado data, or by excluding miners for whom exposure estimates may be less reliable, are very similar. The absence of information on cigarette smoking in the Japanese A-bomb survivors, and the possibility that this may confound the time trends in radiation-induced lung cancer risk in that cohort, imply that these findings should be interpreted with caution. CONCLUSIONS: There are no statistically significant differences between the male A-bomb survivors data and the Colorado miner data in the pattern of variation of relative risk with time after exposure and age at exposure. The risk conversion factor is very close to the value suggested by the latest ICRP lung model, albeit with substantial uncertainties.     

Persistent subclinical inflammation among A-bomb survivors

PURPOSE: To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. SUBJECTS AND METHODS: Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha-1 globulin, alpha-2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. RESULTS: The associations with radiation dose were statistically significant for leukocyte counts (71.0mm(-3) Gy(-1), p=0.015), erythrocyte sedimentation rate (1.58 mm h(-1) Gy(-1) , p = 0.0001), corrected erythrocyte sedimentation rate (1.14mm h(-1) Gy(-1), p=0.0001), alpha-1 globulin (0.0057 g dl(-1) Gy(-1), p=0.0001), alpha-2 globulin (0.0128 g dl(-1) Gy(-1), p=0.0001), and sialic acid (1.2711 mg dl(-1) Gy(-1), p=0.0001) but not for neutrophil counts (29.9 mm(-3) Gy(-1), p=0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. CONCLUSIONS: This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders.     

Cataract in atomic bomb survivors

PURPOSE: Ophthalmologic examinations were conducted on atomic bomb (A-bomb) survivors 55 years after exposure. MATERIALS AND METHODS: A-bomb survivors who had been exposed before 13 years of age at the time of the bombings in 1945 or who had been examined in a previous study between 1978 and 1980. The examinations, conducted between June 2000 and September 2002, included slit-lamp examination, digital photography and a cataract grading system for three parts of the lens (nucleus, cortex and posterior subcapsule) as an outcome variable. Proportional odds logistic regression analysis was conducted using the lowest grading class as a reference and included explanatory variables such as age, sex, city, dose and various cataract-related risk factors. When the grades in an individual differed, the worst grade was used. RESULTS: Results indicate that odds ratios (ORs) at 1 Sv were 1.07 (95% confidence intervals [CI] 0.90, 1.27) in nuclear colour, 1.12 (95% CI 0.94, 1.30) in nuclear cataract, 1.29 (95% CI 1.12, 1.49) in cortical cataract and 1.41 (95% CI 1.21, 1.64) in posterior subcapsular cataract. The same was true after excluding 13 people whose posterior subcapsular cataracts had been previously detected. CONCLUSION: Significant radiation effects were observed in two types of cataracts in A-bomb survivors.     

Persistent subclinical inflammation among A-bomb survivors

Purpose : To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. Subjects and methods : Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, α -1 globulin, α -2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. Results : The associations with radiation dose were statistically significant for leukocyte counts (71.0mm -3 Gy -1, p =0.015), erythrocyte sedimentation rate (1.58mm h -1 Gy -1, p =0.0001), corrected erythrocyte sedimentation rate (1.14 mm h -1 Gy -1, p =0.0001), α -1 globulin (0.0057 g dl -1 Gy -1, p =0.0001), α -2 globulin (0.0128 g dl -1 Gy -1, p =0.0001), and sialic acid (1.2711 mg dl -1 Gy -1, p =0.0001) but not for neutrophil counts (29.9mm -3 Gy -1, p =0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. Conclusions : This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders.     

低剂量辐射诱导免疫适应性反应的实验研究

目的　研究低剂量辐射能否诱导免疫适应性应。方法　３ＨＴｄＲ 掺入法检测淋巴细胞增殖率;ＣＴＬＬ依赖株检测ＩＬ２ 活性;单克隆抗体免疫荧光标记,流式细胞术（ＦＣＭ） 检测淋巴细胞亚组及膜受体表达;ＰＩ标记,ＦＣＭ 检测细胞周期及细胞凋亡;双抗体夹心间接ＥＬＩＳＡ 法测定可溶性白介素２ 受体;Ｆｕｒａ２ 负载,双波长荧光测定法检测细胞内［Ｃａ２＋ ］ｉ;传代培养细胞测定细胞倍增时间。结果　低剂量辐射预照射可明显减轻其后大剂量照射对诸多淋巴细胞功能的抑制作用。结论　低剂量Ｘ 射线可诱导多参数免疫适应性反应。     

Peripheral lymphocyte populations in patients treated with pelvic and mediastinal radiotherapy

Solid tumor bearing patients often show a large variety of immunologic alterations: increase in immune complexes number, reduced NK activity, decreased IL-2 production, T4/T8 reverse and s.o. Most literature data generally concern chemotherapy and/or radiotherapy pretreated patients, so it is difficult to relate the immunological alterations with either antineoplastic treatments or the disease itself. We tried to evaluate any possible alteration of immunological parameters in patients with solid neoplasms who underwent radiotherapy on mediastinum or pelvis. The aim was to detect any variation in peripheral lymphoid sub-populations (even per site of irradiation) and a possible activation of an immune therapy. The evaluable patients were 38 (12 treated with surgery). The minimum dose delivered was 5000 cGys through conventional fractionation. The immunological parameters (T, B, N, T4, T8, H/S) were evaluated before the treatment, at the end and every 2 months during follow-up. Cases were analyzed also per single irradiation volume. No statistically significant variation in immunological parameters was found, although suppressor activity was confirmed as prevailing in immune responsiveness of cancer patients. Thus any significant correlation between immunological state and disease evolution or response to treatment has still to be verified.     

Forthcoming Papers

Summary

A total of 1328 atomic bomb survivors in Hiroshima were studied to determine alterations in the number of blood lymphocytes belonging to T-cell subpopulations, the number of CD19 antigen-positive B cells and the number of Leu 7 and CD16 antigen-positive lymphocytes. Overall, with increasing age, significant decreasing trends in the numbers of some lymphocytes in T-cell subpopulations and of B cells were observed. Furthermore, the number of blood lymphocytes positive for CD5 antigen was significantly lower in the people exposed to radiation (> 1 Gy) in the older age group (more than 30 years old at the time of the bombing). A similar tendency for decreases in the numbers of CD4, CD8, and CD19 antigen-positive cells was observed in these older survivors, although the differences were not statistically significant. These results suggest that aging of the T-cell related immune system is accelerated in the irradiated people of advanced age. This may be explained by the age-related decrease in thymic function in those subjects who were older at the time of the bombing resulting in a decreased functional ability of the immune system after radiation injury. On the contrary, the number of Leu 7 or CD16 antigen-positive cells was found to be increased significantly in the older age group compared to the younger group, although there was little dependence on dose.     

Henry S. Kaplan Distinguished Scientist Award 2003. The crooked shall be made straight; dose-response relationships for carcinogenesis

Estimates of radiation-induced malignancies come principally from the atomic (A)-bomb survivors and show an excess incidence of carcinomas that is linearly related to dose from about 5 cGy to 2.5 Gy. Above and below this dose range there is considerable uncertainty about the shape of the dose-response relationship. Both the International Commission of Radiation Protected (ICRP) and the National Council of Radiation Protection (NCRP) suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. The demonstrated bystander effect for irradiation exaggerates the consequences of small doses of radiation and implies that a linear extrapolation from high doses would underestimate low dose risks. It is possible to make estimates of the cancer risk of diagnostic radiological procedures. Helical computed tomography in children is of particular interest since it is rapidly increasing in use and the doses involved are close to the lower limit of significance in the A-bomb survivors. For example, an abdominal computed tomographic scan in a 1-year-old child can be estimated to result in a lifetime cancer risk of about 1:1000. In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. Data are available for the risk of radiation-induced malignancies for patients who received radiotherapy, e.g. for prostate or cervical cancer. New technologies such as intensity modulated radiation therapy could result in a doubling of radiation-induced second cancers since the technique involves a larger total-body dose due to leakage radiation and the dose distribution obtained involves a larger volume of normal tissue exposed to lower radiation doses.     

Rapid translocation frequency analysis in humans decades after exposure to ionizing radiation.

This paper presents an analysis of the utility of fluorescence in situ hybridization (FISH) with whole-chromosome probes for measurement of the genomic frequency of translocations found in the peripheral blood of individuals exposed to ionizing radiation. First, we derive the equation: Fp = 2.05fp(1-fp)FG, relating the translocation frequency, Fp, measured using FISH to the genomic translocation frequency, FG, where fp is the fraction of the genome covered by the composite probe. We demonstrate the validity of this equation by showing that: (a) translocation detection efficiency predicted by the equation is consistent with experimental data as fp is changed; (b) translocation frequency dose-response curves measured in vitro using FISH agree well with dicentric frequency dose-response curves measured in vitro using conventional cytogenetic procedures; and (c) the genomic translocation frequencies estimated from FISH measurements for 20 Hiroshima A-bomb survivors and four workers exposed to ionizing radiation during the Y-12 criticality accident are approximately the same as the translocation frequencies measured using G-banding. We also show that translocation frequency dose response curves estimated using FISH are similar for Hiroshima A-bomb survivors and for first division lymphocytes irradiated in vitro. We conclude with a discussion of the potential utility of translocation frequency analysis for assessment of the level of acute radiation exposure independent of the time between analysis and exposure.     

Organ doses received by atomic bomb survivors during radiological examinations at the Radiation Effects Research Foundation

When evaluating the risks of oncogenesis and cancer mortality following exposure to the radiations of the atomic bombs (A-bombs), the medical X-ray doses received by the A-bomb survivors must also be estimated and considered. Using a human phantom, dosimetry was performed to estimate the X-ray doses received by A-bomb survivors during medical examinations at the Radiation Effects Research Foundation (RERF) as part of the long-term follow-up on the Adult Health Study (AHS). These examinations have been estimated to represent nearly 45% of the survivors' cumulative medical irradiation dose. Doses to the salivary glands, thyroid gland, lung, breast, stomach and colon were measured using thermoluminescent dosimeters. The results, which are reported here, will aid in estimating organ doses received by individual AHS participants.     

Age-dependent changes in oxygen tension,radiation dose and sensitivity within normal and diseased coronary arteries–Part C: Oxygen effect and its implications on high- and low-LET dose

Purpose: The aim is to study the implications of the decrease in oxygen concentration in the coronary artery walls with age and atherosclerosis, particularly with regard to an associated reduction in the radiosensitivity to high-and low-linear-energy-transfer (LET) irradiation.

Materials and methods: In accompanying papers, the age-dependent morphology and composition for the wall layers of normal and diseased coronary arteries were developed in Part A from published data. In Part B, the oxygen concentration in the coronary artery walls was evaluated taking account the diffusion of oxygen from blood and the solubility of oxygen in tissues. In this part the oxygen effect was evaluated using published experimental data.

Results: Based on simulation results from the one-dimensional diffusion model, the oxygen enhancement ratio (OER) is lower in the hypoxic vessel walls of aged and atherosclerotic arteries. Consequently the high-LET radiation damage arising from both the radon (²²²Rn) and thoron (²²⁰Rn) decay chains to the intimal layer of highly diseased arteries was estimated to be reduced by ～37% due to hypoxia. A greater reduction in radiosensitivity (51%) due to hypoxia was determined for low-LET irradiation.

Conclusion: These results imply that the oxygen effect, and other radiation biological factors, have a significant influence on radiation biological effects and risk of cardiovascular disease (CVD) to Japanese atomic bomb (A-bomb) survivors and patients receiving radiotherapy of the mediastinum.