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During the summers of 1958 and 1959 the increase in concentration of bomb-produced radiocarbon in Denmark was several percent higher than the average increase for the hemisphere. This additional increase is probably a carbon-14 equivalent to the spring peaks in strontium-90 fallout in the North Temperate Zone in the same years, and suggests latitudinal variations in carbon-14 contamination.
We examined the relation between consumption of 22 dietary items and subsequent bladder-cancer incidence in a cohort of atomic-bomb survivors in Japan. Subjects were 38,540 people (14,873 men and 23,667 women) who responded to a mail survey carried out between 1979 and 1981 and who had no known cancer diagnosed before the start of follow-up (1 January 1980 for men, 1 February 1981 for women). Consumption frequencies for 22 dietary items were ascertained with pre-coded answers. As of the end of 1993, there were 114 (83 men and 31 women) incident cases of bladder cancer among 450,326 person-years at risk. Statistical analysis was done using Poisson regression for grouped survival data Consumption of green-yellow vegetables and fruit were protectively associated with risk. Adjusted for gender, age, radiation exposure, smoking status, educational level, body-mass index and calendar time, the relative risk (RR) for those consuming green-yellow vegetables 2-4 times per week and almost everyday was 0.62 [95% confidence interval (CI) 0.39-0.98] and 0.54 (95% CI 0.30-0.94) respectively, as compared with those consuming once per week or less. The corresponding RR for fruit consumption was 0.50 (0.30-0.81) and 0.62 (0.39-0.99) respectively. Chicken consumption was unexpectedly associated with decreased risk, but additional adjustment for consumption did not change the relation of green-yellow vegetables or of fruit to risk. The consumption of the other dietary items, including meat and green tea, was not related to risk. The findings add to evidence that high consumption of vegetables and fruit are protective against bladder cancer.
Generalized relative and absolute risk models, in which various functions of time and age modify the excess relative or absolute risk of radiation-induced cancer, are fitted to the Japanese atomic bomb survivor cancer incidence data set. Among generalized relative risk models, those in which a product of powers of time since exposure and attained age modify the relative risk provide the best fit. There are indications that the Armitage-Doll model (in its formulation as a generalized relative risk model) provides a poor fit to the data, possibly in part because of increasing age-adjusted cancer incidence rates in the Japanese cohort. Generalized absolute risk models, and in particular models in which either powers of time since exposure and attained age, or powers of time since exposure and age at exposure modify the excess absolute risk, provide a superior fit to any of the generalized relative risk models for all solid cancer sites analysed together. When six cancer subtypes are examined separately, only for respiratory cancers does this finding remain true, and for two other sites (female breast cancer and thyroid cancer) the generalized relative risk model yields a better fit than the generalized absolute risk model.
The apparent effect of ionizing radiation on lung cancer in A-bomb survivors has not been large enough to still doubts as to its validity. It has seemed essential to determine whether the apparent radiation effect could have resulted from a confounding of heavy smoking and high radiation dose, or if the occupational exposure of high-dose subjects with lung cancer was suggestive of the influence of environmental hazards other than radiation. The available series consists of 204 subjects with lung cancer verified by autopsy, 61 of whom were low-dose (less than 1 rad) and 13 high-dose (200 + rads) subjects. No evidence could be found that the influence of either smoking or occupational exposure upon lung cancer was exerted so as to suggest that the apparent radiation effect is other than real. The study also provides additional evidence of the relationship between lung cancer and smoking in Japanese.
A panel of Japanese and American pathologists reviewed existing histologic material used to study breast cancer risk among the A-bomb survivors in Hiroshima and Nagasaki, a population in which incidence studies have found a strong relationship between breast cancer risk and radiation dose. The primary charge to the panel was to define a body of confirmed cases in the Life Span Study sample of the Radiation Effects Research Foundation that would require little or no review for inclusion in future studies of breast cancer incidence. Broad agreement on histologic type was reached for 298 of 300 confirmed cases. The distribution of histologic types was, overall, similar to that seen in other studies of breast cancer in Japanese women, and did not appear to depend on dose; thus radiation-induced breast cancer appeared to be no different histologically from other breast cancer. Also, no evidence was found of variation in histologic type by city, age at exposure, age at diagnosis, or calendar time.
The results of surgical treatment of gastric cancer were reviewed retrospectively for 135 atomic bomb survivors and 377 control patients. The mean age was significantly higher in the survivors than in the controls. Otherwise, both groups were quite comparative especially in terms of the stage of the disease. Histopathologically, the rates of poorly differentiated or undifferentiated types of carcinoma and secondary lymph node involvements were significantly lower in the survivors than in the controls. There were no significant difference between the two groups in postoperative morbidity and mortality rates and long-term survival rate. The incidence of second primary malignancies, however, was apparently higher in the survivors than in the controls.
BACKGROUND: Analysis conducted in the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki found a significant dose-related excess of tumors of the central nervous system (CNS) and the pituitary gland. The objective of the current study was to evaluate clinical and epidemiologic characteristics of first primary tumors of the CNS and the pituitary gland in this cohort and to compare them with characteristics among other populations. METHODS: CNS and pituitary gland tumors that were diagnosed between 1958 and 1995 among 80,160 LSS cohort members were ascertained through Hiroshima and Nagasaki tumor registries, autopsy reports, and other sources. Pathologists reviewed all available records and slides to verify histologic diagnoses. Poisson regression analysis was used to model background incidence rates allowing for radiation effects. RESULTS: Meningioma was the most common tumor among clinically diagnosed tumors, followed by neuroepithelial tumor, schwannoma, and pituitary tumor. The overall incidence of these tumors increased initially with age but declined among the elderly. For all age groups and for both genders, incidence increased over time. By contrast, when tumors diagnosed at autopsy were included, incidence rose continuously with age and was stable over time. CONCLUSIONS: The main characteristics of CNS and pituitary gland tumors diagnosed in the LSS cohort were consistent with the characteristics of "spontaneous" tumors observed in other population-based studies. The predominance of meningiomas over neuroepithelial tumors in the Japanese population was noteworthy and warrants further investigation. The secular rise in incidence of all clinically diagnosed CNS and pituitary gland tumors is most likely to be attributable to the increased use of new imaging techniques.
Failure of Notch signaling in zebrafish mind bomb (mib) mutants results in a neurogenic phenotype where an overproduction of early differentiating neurons is accompanied by the loss of later-differentiating cell types. We have characterized in detail the hindbrain phenotype of mib mutants. Hindbrain branchiomotor neurons (BMNs) are reduced in number but not missing in mib mutants. In addition, BMN clusters are frequently fused across the midline in mutants. Mosaic analysis indicates that the BMN patterning and fusion defects in the mib hindbrain arise non-cell autonomously. Ventral midline signaling is defective in the mutant hindbrain, in part due to the differentiation of some midline cells into neural cells. Interestingly, while early hindbrain patterning appears normal in mib mutants, subsequent rhombomere-specific gene expression is completely lost. The defects in ventral midline signaling and rhombomere patterning are accompanied by an apparent loss of neuroepithelial cells in the mutant hindbrain. These observations suggest that, by regulating the differentiation of neuroepithelial cells into neurons, Notch signaling preserves a population of non-neuronal cells that are essential for maintaining patterning mechanisms in the developing neural tube.
After the 1945 atomic bomb explosions, attention was initially drawn to the leukemogenic effect of atomic radiation. Mortality studies over the years have shown that the leukemogenic effect has been gradually declining, and the incidence of solid tumors has been increasing. There was shorter latent period for the appearance of excess leukemia mortality than for solid tumors. It appears that the risk for developing solid tumors becomes greatest when the population enters the age group at which that particular form of cancer most commonly occurs. The leukemogenic and carcinogenic risks are also greater in those exposed to radiation in the younger age groups. There are implications in these studies for cancer control with regard to radiation safety in diagnostic radiology and the peaceful uses of atomic energy; in addition, they emphasize the moral obligation involved in limiting the proliferation of atomic weapons. These observations may also be parallel to the experience of oncologists with second primary cancers after the administration of chemotherapy.
Exposure to ionizing radiation causes damage to living cells, especially to DNA in the cell nucleus. The degree of this cellular damage depends on the amount of radiation administered. This review discusses current findings concerning radiation-induced chromosome aberrations that were produced in 1945 and that can still be observed in the somatic cells of atomic bomb survivors in Hiroshima and Nagasaki. The scoring methods of G-banding and fluorescence in situ hybridization are compared. In addition, some findings concerning chromosomal aberrations in citizens of the former Soviet Union affected by the Chernobyl accident are presented.
Even though vasectomy-associated reactions in subjects are established, the biochemical attributes of the granuloma cells enabling them to potently dispose of the accumulating spermatozoa remain unelucidated. This study demonstrates a careful "free-radical bombing" within the granuloma interior to efficiently disintegrate all the structural elements of the sperm cells, especially the proteins. A free radical triggered and instantaneous protein-disposal could be important in avoiding early post-vasectomy autoimmune triggering.
Cytologic and cytogenetic studies were performed on the bone marrow cells in atomic bomb-exposed patients who had prolonged periods of blood disorders with termination of acute leukemia (group I, 6 cases) and without the termination (group II, 6 cases), and survivors who were in apparent good health (group III, 85 cases). All but one patient in group I, who were examined at the preleukemic state, had abnormal clones. In 4 out of 6 of group I patients, morphologic abnormalities of bone marrow cells taken 3-10 years before leukemic development were found, such as giant neutrophils or basophils, binucleated granulocytes or megakaryocytes, and bridge formation of chromatid in metaphases. All patients in group II had stable types of chromosome aberrations. The types of cytologic abnormalities were similar to those in group I, but the frequencies were a little less than those in group I. In group III, 14 persons were found to have stable types of chromosome aberrations, of which 11 persons had apparent but transient clone formations. Cytologic and clinical abnormalities were not observed in the group. The persistent and high percentages of cytologic and cytogenetic abnormalities in patients with prolonged periods of blood disorders, regardless of history of radiation exposure, would suggest a preleukemic state, and also give some clue to the problems of leukemogenesis.
The present report describes the G-band analysis of somatic chromosomes in lymphocytes from 63 A-bomb survivors in Hiroshima to determine the type and frequency of radiation-induced chromosome aberrations. (1) The cells with stable-type chromosome aberrations (Cs cells) predominated among the aberrant cells, and showed a dose-dependent increase. All stable chromosome aberrations were classified into nine categories: reciprocal translocations, translocations of complex type, insertions, complex exchanges, peri- and paracentric inversions, terminal and interstitial deletions, and unidentified rearrangements. The frequencies of aberrations were found to increase with increasing dose for all aberration categories. Reciprocal translocations predominate in all dose ranges and among the chromosome aberrations classified. (2) The linear model was fitted to test the dose-response relationship for Cs cell frequencies. Employing a constant neutron RBEs of 10, an estimated linear slope of 15.2%/Sv was obtained for DS86 bone marrow dose with an intercept of 2.9% at dose 0. (3) Statistical analysis of data on 3,370 break sites showed good correlations between relative DNA content and the distribution of chromosome breaks involved in translocations, although the involvement of chromosome 1 is significantly higher.
Recently released data on non-cancer mortality in Japanese atomic bomb survivors are analysed using a variety of generalised relative risk models that take account of errors in estimates of dose to assess the dose-response at low doses. If linear-threshold, quadratic-threshold or linear-quadratic-threshold relative risk models (the dose-response is assumed to be linear, quadratic or linear-quadratic above the threshold, respectively) are fitted to the non-cancer data there are no statistically significant ( p>0.10) indications of threshold departures from linearity, quadratic curvature or linear-quadratic curvature. These findings are true irrespective of the assumed magnitude of dosimetric error, between 25%-45% geometric standard deviations. In general, increasing the assumed magnitude of dosimetric error had little effect on the central estimates of the threshold, but somewhat widened the associated confidence intervals. If a power of dose model is fitted, there is little evidence ( p>0.10) that the power of dose in the dose-response is statistically significantly different from 1, again irrespective of the assumed magnitude of dosimetric errors in the range 25%-45%. Again, increasing the size of the errors resulted in wider confidence intervals on the power of dose, without marked effect on the central estimates. In general these findings remain true for various non-cancer disease subtypes.
Generalised absolute risk models were fitted to the latest Japanese atomic bomb survivor cancer incidence data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Because of evidence for irregularities in the low-dose dose response, flexible dose-response models were used, consisting of a linear-quadratic-exponential model, used to model the high-dose part of the dose response, together with piecewise-linear adjustments for the two lowest dose groups. Following an assumed administered dose of 0.001 Sv, lifetime leukaemia radiation-induced incidence risks were estimated to be 1.11 x 10(-2) Sv(-1) (95% Bayesian CI -0.61, 2.38) using this model. Following an assumed administered dose of 0.001 Sv, lifetime solid cancer radiation-induced incidence risks were calculated to be 7.28 x 10(-2) Sv(-1) (95% Bayesian CI -10.63, 22.10) using this model. Overall, cancer incidence risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.
Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93x10(-2) Sv(-1) (95% CI 1.14, 3.38), or 0.44 years of life lost Sv(-1) (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36x10(-2) Sv(-1) (95% CI 8.41, 12.42), or 1.38 years of life lost Sv(-1) (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10-35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.
We derive explicit hazard functions for the clonal expansion model in the "exact formulation" and in the "epidemiological approximation" for the spontaneous rate and for short-time exposure. We investigate which combination of the biological parameters can be determined from the incidence function, and which cannot. We then analyze the incidence data of all solid tumors of atomic bomb survivors (1958-1987). We restrict ourselves to adults at exposure (> 20 years) and to attained age (< 80 years, and we consider the two cities (Hiroshima and Nagasaki) and the two sexes separately. With four parameters, we find good fits in each case, comparable to the quality of fit of epidemiological age-at-exposure and age-attained models used for comparison. The parameters which describe the spontaneous risk agree very well for the two cities, while they are quite different for the two sexes. The apparent flattening of the risk for elderly men can be described with the exact formulation of the clonal expansion model, but may be due to other causes than the mechanisms modeled. The dose-response parameters differ by more than two standard deviations (factor 2 to 3) between the two cities, when considering the same sex. They are bigger of the men of Nagasaki and the women of Hiroshima. One example for model application to tumors of specific organs (men's lung tumor) is considered.
A 48-year-old man was killed by the explosion of a letter bomb after receiving severe injuries to his face and left hand. The autopsy ascertained that the right eye and orbit had been completely destroyed by a large piece of metal from a tin can that had entered the cranial cavity through the right eye and caused fatal brain damage. The victim had also sustained a severe injury to his left hand. Reconstruction of the metal and plastic fragments showed that the victim had received a padded envelope with a video cassette in which a simple explosive device was hidden in a flat tin. The explosive charge consisted of a mixture (ca. 60 g) of sodium chlorate, sodium chloride and sucrose. The charge was detonated by a nylon cord attached to the inside of the envelope which was stretched when the video cassette was pulled out of the envelope. This removed a piece of plastic from between two contacts, and the explosion was set off immediately by a battery which activated two flash bulbs placed within the charge.