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PubMed2002

Absence of evidence for differences in the dose-response for cancer and non-cancer endpoints by acute injury status in the Japanese atomic-bomb survivors.

PURPOSES: To ascertain possible evidence for radiosensitive subgroups in the Japanese atomic-bomb survivors. MATERIALS AND METHODS: Time- and age-adjusted relative risk models were fitted to the Japanese atomic-bomb survivor mortality data, taking account of the modifying effects of acute injury status and adjusting for random dosimetric errors. RESULTS: For leukaemia, there were statistically significantly higher relative risks among those persons reporting either epilation (two-sided p=0.03) or burns (two-sided p=0.02), but after adjustment is made for the effects of dosimetric error these results become statistically non-significant (two-sided p>0.05) For all other endpoints (cancers other than leukaemia, benign neoplasms, cardiovascular disease, non-cancer and non-cardiovascular disease) there were no statistically significant modifying effects on relative risk of acute injury status, whether or not adjustment is made for the effects of dosimetric error. CONCLUSIONS: Apart from leukaemia, there are generally no indications for cancer or other disease endpoints of variations in dose-response by acute injury status. The increased risks observed for leukaemia among those reporting epilation or burns are much diminished after adjustment for dosimetric error, and so there is no strong evidence of a sensitive subgroup within the Life Span Study cohort.

Acute Disease↗
PubMed1996

Chromosome aberration analysis in atomic bomb survivors and Thorotrast patients using two- and three-colour chromosome painting of chromosomal subsets.

Chromosomal translocations in peripheral lymphocytes of three healthy Hiroshima atomic (A)-bomb survivors, as well as three Thorotrast patients and two non-irradiated age-matched control persons from the German Thorotrast study were studied by two- and three-colour fluorescence in situ hybridization (chromosome painting) with various combinations of whole chromosome composite probes, including chromosomes 1, 2, 3, 4, 6, 7, 8, 9 and 12. Translocation frequencies detected by chromosome painting in cells of the A-bomb survivors were compared with results obtained by G-banding. A direct comparison was made, i.e. only those cells with simple translocations or complex aberrations detected by G-banding were taken into consideration which in principle could be detected also with the respective painting combination. The statistical analysis revealed no significant differences from a 1:1 relationship between the frequencies of aberrant cells obtained by both methods. The use of genomic translocation frequencies estimated from subsets of chromosomes for biological dosimetry is discussed in the light of evidence that chromosomes occupy distinct territories and are variably arranged in human lymphocyte nuclei. This territorial organization of interphase chromosomes implies that translocations will be restricted to chromatin located at the periphery of adjacent chromosome territories.

Aged↗
PubMed1997

The risk of non-melanoma skin cancer incidence in the Japanese atomic bomb survivors.

The latest Japanese atomic bomb survivor non-melanoma skin cancer incidence dataset is analysed and indicates substantial curvilinearity in the dose-response curve, consistent with a possible dose threshold of about 1 Sv, or with a dose-response in which the excess relative risk is proportional to the fourth power of dose, with a turning-over in the dose-response at high doses (> 3 Sv). The time distribution of the radiation-induced excess risk is best described by a model in which the relative excess risk is proportional to a product of powers of time since exposure and attained age. The fits of generalized relative risk models with exponential functions of time and age at exposure (and in particular of attained age) to adjust the relative risk are less satisfactory, as also are the fits of other models in which products of powers of time since exposure, age at exposure and attained age adjust the excess absolute risk. Sensitivity analyses indicate the importance of likely adjustments to the Hiroshima neutron doses for the optimal model parameters, particularly if values of the neutron relative biological effectiveness (RBE) of more than 5 are assumed. If adjustments recently proposed are made to the Hiroshima neutron doses, then using the optimal model (in which excess risk is proportional to the fourth power of dose) the best estimate of the neutron RBE is 1.3 (95% CI < 07.1). However, uncertainties in skin dose estimates for the atomic bomb survivors means that the findings with respect to the neutron RBE and the non-linearity in the dose-response curve should be treated with caution.

Dose-Response Relationship, Radiation↗
PubMed1998

Curvature in the cancer mortality dose response in Japanese atomic bomb survivors: absence of evidence of threshold.

PURPOSES: To investigate the evidence for a threshold in the cancer dose-response curve. MATERIALS AND METHODS: Japanese atomic bomb survivor cancer mortality data, based on follow-up to 1990, was used, taking account of random errors in DS86 dose estimates. RESULTS: For all solid cancers analysed together, there is a significant positive dose response (two-sided p<0.05) if all survivors who received <0.5 Sv are considered, but the significance vanishes if doses of <0.2 Sv are considered; the same is also true for leukaemia. For solid cancer mortality there is no indication of curvilinearity in the dose response: no statistically significant improvement in fit to a linear relative risk model is provided by addition of quadratic or threshold dose terms. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer mortality data, the best estimate of the threshold is < 0.00 Sv (95% CI <0.00-0.13). If a linear-quadratic-threshold model is used the best estimate of the threshold is < 0.00 Sv (95% CI < 0.00-0.15). For leukaemia mortality there is highly statistically significant upward curvature in the dose response. In particular, if a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukaemia data, the best estimate of the threshold is 0.16 Sv (95% CI 0.05-0.40) (two-sided p=0.001 for test of departure of threshold from 0). However, there is no evidence for a threshold effect (two-sided p = 0.16) when a quadratic term is included in the dose response: the best estimate of threshold in this case is 0.09Sv (95% CI <0.00-0.29). Moreover, addition of a quadratic term improves the fit of a linear-threshold model at borderline levels of statistical significance (two-sided p = 0.07). Therefore, the most parsimonious description of the leukaemia dose response is provided by a linear-quadratic function of dose. CONCLUSIONS: There is no evidence of threshold-type departures from the linear-quadratic dose response either for solid tumours or for leukaemia in the Japanese atomic bomb survivor mortality data.

Dose-Response Relationship, Radiation↗
PubMedDate not supplied

The impact on civilians of the bombing of Kosovo and Serbia.

Before the 1999 bombing, Kosovo was among the poorest regions in Europe, with low scores on indices of health care. After the war, housing for much of the population is below even basically acceptable standards and health care is disrupted, with serious risk of epidemic diseases. Societal disintegration has led to high levels of stress. In Serbia, also a poor country, which already suffered from high levels of pollution before the war, large amounts of several highly toxic chemicals were liberated into the environment by the bombing. Targeting of electrical generating plant, water treatment facilities, Danube bridges, railways and roads has adverse effects on civilian life, endangers health and seriously affects health care. The military strategy of attack on civilian infrastructures is a war on public health.

Adolescent↗
PubMedDate not supplied

Present status and self-reported diseases of the Korean atomic bomb survivors: a mail questionnaire survey.

Many Koreans were forced to move to Japan while Korea was occupied by Japan. Consequently, when the atomic bombs were dropped on Hiroshima and Nagasaki an estimated 40,000 Koreans died and 30,000 survived. In 2004, 2,235 Koreans were registered as A-bomb survivors in South Korea. A mail questionnaire survey to evaluate the present status and self-reported diseases of the Korean survivors was conducted. In total, 1,256 questionnaires were returned and analysed. The most frequent chronic diseases reported by Korean survivors were hypertension (40.1 per cent), peptic ulcer disease (25.7 per cent), anaemia (23.3 per cent) and cataracts (23.1 per cent). The most frequent malignant diseases were stomach cancer (1.9 per cent), colon cancer (0.5 per cent) and leukaemia/multiple myeloma (0.4 per cent). This study suggests that further investigations are needed into the health concerns of the survivors and into health protection measures.

Aged↗
PubMedDate not supplied

The consumption bomb.

The explosion of the population bomb has long been predicted to cause massive famine in overpopulated countries. Rising consumption, even in a time of decreasing population growth rates, now threatens adverse global health effects more severe than localised famines. The world faces potential ecological entrapment. This has two dimensions: planetary eco-impoverisation and planetary eco-pathology. Eco-impoverisation, the depletion of natural capital, arises as the limit of the global human carrying capacity approaches. Eco-pathology, the disruption of ecological support systems, arises because of the way the biosphere has been modified by human activity and is caused particularly by unsustainable consumption for human purposes. Despite encroaching ecological entrapment, the dominant economic paradigm claims record levels of growth; a paradox that needs recognition. Reasons for denial of the gravity of ecological entrapment are discussed. Ways are suggested to defuse the consumption bomb and avert ecological entrapment.

Conservation of Natural Resources↗
PubMed2004

The ethics of self-sacrifice: what's wrong with suicide bombing?

What's wrong with suicide bombing? The tactic has been used by the Tamil Tigers, by the Japanese kamikaze, by al-Qaeda, by Palestinian militants against Israel, by Iraqi defenders loyal to Saddam Hussein against the U.S. invasion, and by others; it is typically understood by these groups as martyrdom rather than suicide. Scientific theories of suicide--biological, psychological, and sociological--do not contribute to an understanding. Nor is the claim that it is amoral, the product of psychopathology or mental illness, adequate. The central moral core of the issue of suicide bombing rests, rather, on the violation of a tacit assumption of equality in combat: "they" have a weapon "we" don't.

Journal Article↗
PubMed2006

Molecular basis of basal cell carcinogenesis in the atomic-bomb survivor population: p53 and PTCH gene alterations.

Epidemiological studies suggest that UV exposure from sunlight is the major etiology for skin cancers, both melanocytic and non-melanocytic. However, the radiation-related risk for skin cancer among atomic bomb survivors of Hiroshima and Nagasaki is primarily derived from the excess risk of basal cell carcinoma (BCC), with no demonstrable excess in squamous cell carcinoma or melanoma. The BCCs in this cohort are therefore unusual in being potentially attributable to two types of radiation-UV and ionizing (IR). BCCs have been associated with PTCH and/or p53 tumor suppressor gene alterations. To investigate the roles of these genes in relation to IR and UV exposures, we analyzed both genes in BCC samples from atomic bomb survivors. We examined 47 tumors, of which 70% had non-silent base-substitution p53 mutations independent of IR or UV exposure. However, the distribution of mutation type depends on UV and/or IR exposure. For example, C-to-T transitions at CpG sites adjacent to pyrimidine-pyrimidine (PyPy) sequences were more prevalent in tumors from UV-exposed than UV-shielded body areas and CpG-mutations at non-PyPy sequences were more prevalent in tumors from UV-shielded body areas with high-IR (>or=1 Gy) than low-IR (<0.2 Gy) exposure. And notably, although p53 deletion-frequencies demonstrated no IR-dose associations, deletions at the PTCH locus were more frequent (79% versus 44%) in tumors with high-IR than low-IR exposure. Moreover, 60% of high-IR tumors harbored both p53 and PTCH abnormalities compared with 23% of low-IR tumors. Therefore, alteration of both genes is likely to play a role in radiation-induced basal cell carcinogenesis.

Basal Cell Carcinoma↗
PubMed2002

Evolutionary genetic models of the ovarian time bomb hypothesis for the evolution of genomic imprinting.

At a small number of loci in eutherian mammals, only one of the two copies of a gene is expressed; the other is silenced. Such loci are said to be "imprinted," with some having the maternally inherited allele inactivated and others showing paternal inactivation. Several hypotheses have been proposed to explain how such a genetic system could evolve in the face of the selective advantages of diploidy. In this study, we examine the "ovarian time bomb" hypothesis, which proposes that imprinting arose through selection for reduced risk of ovarian trophoblastic disease in females. We present three evolutionary genetic models that incorporate both this selection pressure and the effect of deleterious mutations to elucidate the conditions under which imprinting could evolve. Our findings suggest that the ovarian time bomb hypothesis can explain why some growth-enhancing genes active in early embryogenesis [e.g., mouse insulin-like growth factor 2 (Igf2)] have evolved to be maternally rather than paternally inactive and why the opposite imprinting status has evolved at some growth-inhibiting loci [e.g., mouse insulin-like growth factor 2 receptor (Igf2r)].

Animals↗
PubMed1974

Mortality in the children of atomic bomb survivors and controls.

A continuing study of mortality rates among children born to survivors of the atomic bombings and a suitable group of controls has been updated; the average interval between birth and verification of death or survival is 17 years. The mortality experience is now based on 18,946 children liveborn to parents one or both of whom were proximally exposed, receiving jointly an estimated dose of 117 rem; 16,516 children born to distally exposed parents receiving essentially no radiation; and 17,263 children born to parents not in Hiroshima or Nagasaki at the time of the bombings. No clearly significant effect of parental exposure on child's survival can be demonstrated either by a contingency chi(2) type of analysis or regression analysis. On the basis of the regression data, the minimal gametic doubling dose of radiation of this type for mutations resulting in death during (on the average) the first 17 years of life among liveborn infants conceived 0-13 years after parental exposure is estimated at 46 rem for fathers and 125 rem for mothers. On the basis of experimental data, the gametic doubling dose for chronic, low-level radiation would be expected to be three to four times this value for males and as much as 1000 rem for females.

Adolescent↗
PubMed2002

Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure.

BACKGROUND: The risk of developing nervous system tumors following exposure to ionizing radiation is not well quantified. We characterized the incidence of nervous system tumors among atomic bomb survivors as a function of radiation dose. METHODS: Tumors of the nervous system and pituitary gland diagnosed between 1958 and 1995 among 80 160 atomic bomb survivors were ascertained using the Hiroshima and Nagasaki tumor registries, medical records, and death certificates. Pathologists reviewed slides and medical records to provide histologic diagnoses. Poisson regression analyses were used to characterize radiation effects on tumor incidence, which are expressed as excess relative risk per sievert (ERR(Sv)). All statistical tests were two-sided. RESULTS: A statistically significant dose-related excess of nervous system tumors was observed in the cohort (ERR(Sv) = 1.2, 95% confidence interval [CI] = 0.6 to 2.1). The highest ERR(Sv) was seen for schwannoma (4.5, 95% CI = 1.9 to 9.2). The risk for all other nervous system tumors as a group is also statistically significantly elevated (ERR(Sv) = 0.6, 95% CI = 0.1 to 1.3). Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5). The dose-response relationships were linear. For nervous system tumors other than schwannoma, excess risks were higher for men than for women and for those exposed during childhood than for those exposed during adulthood. CONCLUSIONS: A statistically significant dose response was observed for all nervous system tumors combined and for schwannoma considered separately, indicating that exposure to even moderate doses (i.e., <1 Sv) of radiation is associated with an elevated incidence of nervous system tumors.

Adult↗
PubMed1975

Frequency of marriage and live birth among survivors prenatally exposed to the atomic bomb.

Frequency of marriage and birth as of January 1973 was determined for persons exposed in utero to the atomic bombs in 1945 and for controls. The marriage rate was lower in persons heavily exposed in utero than in the non-exposed or lightly exposed. This difference is attributed partly to the lesser marriageability of persons with mental retardation who are significantly more numerous among the heavily exposed, and partly to unmeasured variables, possibly including social discrimination against survivors of the atomic bomb. No consistent relation was observed between radiation exposure and three reproductive indices: childless marriages, number of births, and interval between marriage and first birth.

Adult↗
PubMed1989

The 1986 terrorist bombing experience in Paris.

Between December 7, 1985 and September 17, 1986, eleven terrorist bomb explosions took place in Paris. Thirteen people died immediately, 255 others were injured. Forty were treated on-site and were not hospitalized, 205 were subjected to triage and stabilization and were then hospitalized. These latter 205 patients are analyzed in this study. None of them died during transportation, and seven eventually died in hospitals. Forty-seven per cent of all victims suffered from multiple injuries. All deaths except one occurred in the polytraumatized group. The policy of subjecting victims of terrorist bomb explosions to triage and stabilization before hospitalization is compared to the so-called "scoop and run" technique, more generally applied in mass casualty situations. Its limitations and advantages are discussed.

Adult↗
PubMed1987

Europium-152 depth profile of a stone bridge pillar exposed to the Hiroshima atomic bomb: 152Eu activities for analysis of the neutron spectrum.

The 152Eu activity depth profile of a granite pillar of the Motoyasu bridge located 132 m from the Hiroshima atomic bomb hypocenter was assessed. The pillars each measured 82 cm in depth, 82 cm in width and 193 cm in height. One of the pillars was bored and 6.8-cm-diameter core samples were removed and cut into 2-cm-thick disks. Two gamma rays of 152Eu, 122 keV and 344 keV, in each disk were measured using a low background, gamma-ray spectrometer, and the activity distribution was determined as a function of depth in the granite. A concentration of stable Eu in the granite was determined by activation analysis. The specific radioactivity of 152Eu and 154Eu at the pillar surface was determined to have been 117 and 24 Bq per mg Eu, respectively, at the time of detonation. The value of 152Eu agrees within 20% of that calculated by Loewe. The depth profile of 152Eu in granite demonstrates a distinct difference from the estimates made only by thermal neutrons. Present data provide valuable information for the analysis of the neutron spectrum of the Hiroshima atomic bomb and its intensity.

Europium↗
PubMed1994

Benchmark test of neutron transport calculations: indium, nickel, gold, europium, and cobalt activation with and without energy moderated fission neutrons by iron simulating the Hiroshima atomic bomb casing.

A benchmark test of the Monte Carlo neutron and photon transport code system (MCNP) was performed using a bare- and energy-moderated 252Cf fission neutron source which was obtained by transmission through 10-cm-thick iron. An iron plate was used to simulate the effect of the Hiroshima atomic bomb casing. This test includes the activation of indium and nickel for fast neutrons and gold, europium, and cobalt for thermal and epithermal neutrons, which were inserted in the moderators. The latter two activations are also to validate 152Eu and 60Co activity data obtained from the atomic bomb-exposed specimens collected at Hiroshima and Nagasaki, Japan. The neutron moderators used were Lucite and Nylon 6 and the total thickness of each moderator was 60 cm or 65 cm. Measured activity data (reaction yield) of the neutron-irradiated detectors in these moderators decreased to about 1/1,000th or 1/10,000th, which corresponds to about 1,500 m ground distance from the hypocenter in Hiroshima. For all of the indium, nickel, and gold activity data, the measured and calculated values agreed within 25%, and the corresponding values for europium and cobalt were within 40%. From this study, the MCNP code was found to be accurate enough for the bare- and energy-moderated 252Cf neutron activation calculations of these elements using moderators containing hydrogen, carbon, nitrogen, and oxygen.

Cobalt↗
PubMed1996

Estimation of radiation doses for atomic-bomb survivors in the Hiroshima University Registry.

The present study presents the Hiroshima University Registry of atomic bomb survivors, of which the total number is about 270,000, and application of absorbed doses. From this registry, we picked up 49,102 survivors and applied organ doses based on the dosimetry system 1986 (DS86), which is named the Atomic Bomb Survivor 1993 Dose (ABS93D). The applied dose data are based on the tables listed in the DS86 final report such as the free-in-air kermas, the house shielding factors, and organ dose factors for the active bone marrow and the breast. Calculations for the 13 other organs provided in DS86 are possible. To obtain the organ doses for each survivor, it is necessary to obtain information concerning (1) place exposed, (2) whether they were shielded or not, and (3) age. ABS93D body transmission factors for active bone marrow for neutrons and gamma rays agreed with DS86 to within a few percent. Of the survivors studied, 35,123 of them were used for the relative risk estimation of leukemia mortality, adopting the same method as the Radiation Effects Research Foundation (RERF) for comparison. For the observation period from 1968 to 1989, the analyzed relative risks for leukemia mortality at 1 Gy by shielded kerma and by active bone marrow dose are 2.01 and 2.37, respectively, which are consistent with the RERF results.

Dose-Response Relationship, Radiation↗
PubMed1997

Evaluation of possible population bias among high-dose atomic bomb survivors in the frequency of the HLA-DQA1 allele and DR antigen types.

Many studies have suggested a relationship between certain alleles of the human leukocyte antigen (HLA) and the prevalence of some diseases or the immunological responsiveness to certain antigens. Furthermore, our studies in the past have demonstrated decreased immune function among atomic-bomb survivors who were exposed to high doses of radiation. However, no studies have addressed the possibility of various degrees of radiation-induced immune suppression being dependent on HLA type. To investigate the possibility of differing frequency distributions of HLA type in the Hiroshima atomic bomb survivors, HLA-DQA1 alleles and HLA-DR antigens were typed for 291 survivors in a high-dose group (>1.5 Gy), 339 survivors in an intermediate-dose group (0.005-1.5 Gy), and 388 in a distally exposed control group (<0.005 Gy). These doses are whole-body exposures, mainly from gamma-rays but with a small neutron component. When examinees were grouped by distinct pairs of HLA-DQA1 allele or HLA-DR antigen, no sex- or dose-related differences were found. However, when subjects were grouped by the presence of a specific allele or antigen, males carrying DQA1*0103 in at least one of their two HLA-DQA1 loci exhibited frequency distributions that decreased as radiation dose increased. These results suggest, although weakly, a possible population bias among male survivors with respect to HLA polymorphism. However, this bias is unlikely to be great enough to have a substantial effect on the cancer risk estimates.

Adolescent↗