[en] If we exclude all persons who were classified as clerical workers we find that over 40% of the Hanford workers had either professional or technical qualifications (professional workers). The ratio of professional to manual workers was equally high for safe and dangerous occupations but during the period 1944-77 professional workers who were doing the most dangerous work had too many deaths by comparison with other persons with similar qualifications, and manual workers doing equally dangerous work had too few deaths by comparison with other manual workers. In practice, this means that in any analysis of dose-related cancer risks of Hanford workers it is essential to control for job-related mortality risks as well as all the usual factors such as sex, dates of birth and hire and duration of employment. The results of including all these factors in a cohort analysis of Hanford data by the method of regression models in life tables are described and also the reasons why it was concluded that the risk per unit dose is increased at low dose levels (i.e. the dose-response curve is curvilinear downwards). (author)

[en] The methods employed in evaluating radiological risk are based, by and large, on the non-threshold linear relationships proposed by the ICRP and the Advisory Committee on the Biological Effects of Ionizing Radiations (BEIR) of the US Academy of Sciences in its 1972 report. Recently, the contentious discussions surrounding the latest BEIR report and the publication of new estimates of the doses received at Hiroshima and Nagasaki have reopened the controversy surrounding dose-effect relationships. The chief point at issue is the shape of this relationship - whether or not it is linear and whether it has a threshold - and the role of radiation in carcinogenesis, both in association with other risk factors and as an independent factor. The present paper leaves the theoretical questions aside and instead shows how, by marshalling information on irradiated human populations, a sequence of calculations can be set up to enable specialists to assign numerical values to the coefficients for these relationships. In an empirical approach such as this, theoretical hypotheses are no longer the sole factors at work. Comparatively pragmatic choices, such as the sample on the basis of which the curves are adjusted, the survival tables used, or even the simplifications made in taking account of sex and age, can also influence the result obtained. Sensitivity analyses are presented for the value of the coefficient of cancer induction per unit dose, showing that controversial theoretical options such as the transformation of a linear into a quadratic linear relationship have no greater effect on the result than other more contingent choices. Lastly, the implications of these sensitivity analyses for the practical application of dose-risk relationships are examined in relation to impact studies, optimization procedures, etc. (author)

[en] Cell killing by gamma rays was studied in Heteracris littoralis. Primary spermatocytes, which are encysted and have cytoplasmic connection, show unusual dose-response kinetics with no shoulder at low doses. Also, the spermatocytes do not die independently but in groups, usually with whole cysts degenerating synchronously. (author)

[en] Analysis was performed on the relationships between the organ dose-equivalent rate due to natural background radiation (mSv/a) and three parameters of cancer risk: the age-adjusted cancer incidence (patients x 10⁵ persons x a^-1) in 13 large areas, the standardized mortality ratio of cancers in 46 large areas, and the cancer mortality in the population aged more than 40 years old (cancer deaths x 10⁵ persons x a^-1) in 649 small areas. The age-adjusted liver cancer incidence in males fitted the exponential model significantly (p<0.01) and the relationship of stomach cancer mortality of aged males in small areas fitted the linear model significantly (p<0.05). No relationship was observed with regard to female cancer in either case. The relationships between the three parameters and various other cancers of both sexes were not statistically significant. (author)

[en] It can be stated with confidence that there are a number of factors involved in the etiology of cancer, genotoxic ''pollution'' being one of them. Ionizing radiation is one of the factors involved, but the important role played by various chemical products must not be forgotten. Ethylene oxide (EO) is particularly noteworthy in this connection as an alkylating agent, a mutagen and probably also a carcinogen. This gas is used very widely in the chemical industry and also in cold sterilization and disinfection processes. Measurements of the atmospheric concentration of EO have been carried out systematically over short or long periods in four sterilization plants of different capacities. A work study was conducted on 27 persons exposed to the gas every day. In conjunction with atmospheric data and the rad-equivalence principle, the information obtained from the study was used to evaluate their annual occupational exposure, the level of which proved to be high. Biological surveillance of the subjects exposed offers a possible method of checking this evaluation and of monitoring personnel. The alkylation rate of various haemoglobin amino acids can be measured in this way, but here difficulties arise in collecting the necessary blood samples. (author)

[en] Whole-body gamma or neutron irradiation of mice with 0.01 Gy or even less causes a reduction of uptake of ³H-thymidine and ¹²⁵I-deoxyuridine into bone marrow cells, and concordantly an elevation of thymidine in the blood serum. The effects are at maximum at 4 h and subside about 10 h after exposure. To further elucidate this phenomenon, bone marrow cells were obtained at various times after whole-body exposure and incubated in vitro using different media, buffers and pH ranges. Thymidine kinase was assayed in high-speed supernatant of cell homogenates, again with different conditions of buffer and pH. Bone marrow cells from sham-irradiated mice served as controls. Tracer uptake into bone marrow cells in vitro following irradiation in vivo is depressed when the cells are collected in TC-199 medium buffered to pH 7.2-7.4 with NaHCO₃, 1.350 mg/L medium. Outside this pH range and without NaHCO₃, tracer uptake is not depressed. Concordant with depression of tracer uptake, thymidine kinase was found to be inhibited, yet beyond a dose of 0.01 Gy the effect was dose-independent and 35% of the thymidine kinase remained uninhibited. There was no inhibition when intact cells were collected outside the optimal pH range and in the absence of NaHCO₃. Addition of NaHCO₃ to cellular homogenate or supernatant failed to restore enzyme inhibition. Procain chloride given to the mice 1 h before to 1 h after irradiation fully abolished the depression of tracer uptake into cells in vitro. The effect described is produced by very few or single-cellular radiation-absorption events. It may be a physiological answer of hit cells to background radiation and may influence the effect from chronic low dose-rate exposure. (author)

[en] On the basis of a general descriptive framework which takes into account the intensity factor and the time distribution of radiation, a detailed justification for which is to be found in earlier publications, the three fundamental problems mentioned in the title of this paper can be approached in a new way. If the biological effect e for a given dose D delivered at different radiation intensities phi is studied, we find that the curve e=f(phi) can exhibit non-monotonic shapes. This type of phenomenon is known in pharmacology and toxicology and may well exist also for low- or medium-intensity radiation effects. Extrapolation of the effects of a given dose between high and low radiation intensities phi is usually carried out by means of an empirical linear or linear-quadratic formulation. This procedure is insufficiently justified from a theoretical point of view. It is shown here that the effects can be written in the form e=k(phi)D and that the factor of proportionality k(phi) is a generally very complicated function of phi. Hence, the usual extrapolation procedures cannot deal with certain ranges of values of phi within which the effects observed at a given dose may be greater than when the dose is delivered at higher intensity. The problem of thresholds is actually far more difficult than the current literature on the subject would suggest. It is shown here, on the basis of considerations of qualitative dynamics, that several types of threshold must be defined, starting with a threshold for the radiation intensity phi. All these thresholds are interrelated hierarchically in fairly complex ways which must be studied case by case. These results show that it is illusory to attempt to define a universal notion of threshold in terms of dose. The conceptual framework used in the proposed approach proves also to be very illuminating for other studies in progress, particularly in the investigation of phenomena associated with ageing and carcinogenesis. (author)

[en] Investigations on unscheduled DNA synthesis (UDS) in lymphocytes of persons chronically exposed to low doses of high-LET radiation by inhalation of ²²²Rn and its daughters revealed an enhanced repair capability for DNA damage. This study was performed to ascertain these previous findings and, in addition, to determine the frequency of spontaneously occurring and Mitomycin C (MMC) induced sister chromatid exchanges (SCE) in the lymphocytes of exposed persons. Thirty-five people, occupationally exposed to various low levels of gamma radiation, were tested. For measurement of UDS, lymphocytes were separated from whole blood by Ficoll-Urografin centrifugation, irradiated by 20 J/m² UV of 254 nm, and ³H-thymidine incorporation followed by autoradiography after 90 min of repair incubation. Statistical analysis of the results obtained demonstrated a significant increase of UDS in persons exposed to >14 mrad/month. SCEs were determined in lymphocytes cultured in the presence of 10^-6 mol/L bromodeoxyuridine and with and without 10^-7 mol/L MMC for 72 h. Spontaneously occurring SCEs did not show any dependence on radiation exposure of test subjects, while reduced rates of MMC induced SCEs were demonstrated in lymphocytes from people exposed to doses >14 mrad/month. To examine whether a shift within the lymphocytic cell population would contribute to the observed changes in the capability for repair of UV and MMC induced DNA damage, the percentage of spontaneous T rosettes was determined; no difference between exposed and unexposed persons could be found. The increase of repair incorporation after chronic low-dose exposure could be attributed to an induction of de novo synthesis of repair enzymes

[en] These studies address first the effect of single small doses of X-rays upon murine haematopoietic stem cells to obtain a better estimate of the Dsub(q). It is small, of the order of 20 rad. Second, a dose fractionation schedule that does not kill or perturb the kinetics of haematopoietic cell proliferation was sought to investigate the leukaemogenic potential of low-level radiation upon an unperturbed haematopoietic system. Doses used by others in past radiation leukaemogenesis studies clearly perturb haematopoiesis and kill a detectable fraction of stem cells. The studies reported in the paper show that 1.25 rad every day decreases the CFU-S content of bone marrow by the time 80 rad are accumulated. Higher daily doses as used in published studies on radiation leukaemogenesis produce greater effects. Studies of the effect of 0.5, 1.0, 2.0 and 3.0 rad three times per week are under way. Two rad three times per week produce a modest decrease in CFU-S content of bone marrow after an accumulation of 68 rad. With 3.0 rad three times per week, an accumulation of 102 rad produces a significant decrease in CFU-S content of bone marrow. Dose fractionation at 0.5 and 1.0 rad three times per week has not produced a CFU-S depression after accumulation of 17 and 34 rad. Radiation leukaemogenesis studies published to date have used single doses and chronic exposure schedules that probably have significantly perturbed the kinetics of haematopoietic stem cells. Whether radiation will produce leukaemia in animal models with dose schedules that do not perturb the kinetics of haematopoietic stem cells remains to be seen. (author)

[en] The radiotoxicity of ¹²⁵I incorporated into DNA is extremely high. This has been attibuted to the emission of Auger electrons, resulting in high ionizing density close to the decay. Triiodothyronine (T3) binds to a high affinity, low capacity nuclear receptor close to DNA. ¹²⁵I-T3 induces serious DNA damage in GHl cells and results in the accumulation of several DNA strand breaks per ¹²⁵I decay. The D₀ of V79 cells after ¹²⁵I-T3 treatment was found to be 750 ¹²⁵I decays per cell, corresponding to less than 375 ¹²⁵I decays per cell nucleus. (author)