The effect of low-dose ionizing radiation exposure on leukemia incidence remains poorly understood. Possible dose-response curves for various forms of leukemia are largely based on cohorts of atomic bomb survivors. Animal studies can contribute to an improved understanding of radiation-induced acute myeloid leukemia (rAML) in humans. In male CBA/H mice, incidence of rAML can be described by a two-hit model involving a radiation-induced deletion with Sfpi1 gene copy loss and a point mutation in the remaining Sfpi1 allele. In the present study (historical) mouse data were used and these processes were translated into a mathematical model to study photon-induced low-dose AML incidence in male CBA/H mice following acute exposure. Numerical model solutions for low-dose rAML incidence and diagnosis times could respectively be approximated with a model linear-quadratic in radiation dose and a normal cumulative distribution function. Interestingly, the low-dose incidence was found to be proportional to the modeled number of cells carrying the Sfpi1 deletion present per mouse following exposure. After making only model-derived high-dose rAML estimates available to extrapolate from, the linear-quadratic model could be used to approximate low-dose rAML incidence calculated with our mouse model. The accuracy in estimating low-dose rAML incidence when extrapolating from a linear model using a low-dose effectiveness factor was found to depend on whether a data transformation was used in the curve fitting procedure.

A biologically based two-stage carcinogenesis model is applied to epidemiological data for lung cancer mortality in a large uranium miner cohort of the WISMUT company (Germany). To date, this is the largest uranium miner cohort analyzed by a mechanistic model, comprising 35,084 workers among whom 461 died from lung cancer in the follow-up period 1955-1998. It comprises only workers who were first employed between 1955 and 1989 and contains information on annual exposures to radon progeny. We fitted the model's free parameters, including the average growth time of one malignant cell into a lethal tumor. This lag time has an extraordinary value of 13 to 14 years, larger than that previously used or found in miner studies. Even though cohort-wide information on smoking habits is limited and the calendar-year dependence of tobacco smoke exposure was only implicitly accounted for by a birth cohort effect, we find good agreement between the modeled (expected) and empirical (observed) lung cancer mortality. Model calculations of excess relative lung cancer death risk agree well with those from the descriptive, BEIR VI-type exposure-age-concentration model for WISMUT miners. The large variety of exposure profiles in the cohort leads to a well-determined mechanistic model that in principle allows for an extrapolation from occupational to indoor radon exposure.

From studies of the atomic bomb survivors, it is well known that ionizing radiation causes several forms of leukemia. However, since the specific mechanism behind this process remains largely unknown, it is difficult to extrapolate carcinogenic effects at acute high-dose exposures to risk estimates for the chronic low-dose exposures that are important for radiation protection purposes. Recently, it has become clear that the induction of acute myeloid leukemia (AML) in CBA/H mice takes place through two key steps, both involving the Sfpi1 gene. A similar mechanism may play a role in human radiation-induced AML. In the present paper, a two-mutation carcinogenesis model is applied to model AML in several data sets of X-ray- and neutron-exposed CBA/H mice. The models obtained provide good fits to the data. A comparison between the predictions for neutron-induced and X-ray-induced AML yields an RBE for neutrons of approximately 3. The model used is considered to be a first step toward a model for human radiation-induced AML, which could be used to estimate risks of exposure to low doses.

Radon and thoron progenies in Dutch dwellings cause ~400 cases of lung cancer per year. Some 30% of the risk is due to thoron progeny, which demonstrates that the influence of thoron progeny is much larger than previously anticipated. This was concluded from a national survey in 2500 Dutch dwellings, built since 1930. Radon concentrations (15.6 ± 0.3 Bq m-3 on average) are correlated to type of dwelling, year of construction, ventilation system, location (soil type) and smoking behaviour of inhabitants. The survey data support the establishment of a comparatively low national reference level for radon in dwellings in the Netherlands of 100 Bq m-3, in line with recommendations by WHO and ICRP. Some 24 thousand of the 6.2 million dwellings in the Netherlands (built since 1930) are expected to exceed this level. Around 80% of these are located in the relatively small group of naturally ventilated single-family houses in two designated geographical areas. Radon concentrations above 200 Bq m-3 are rare in the Netherlands and simple and inexpensive measures will be sufficient to reduce enhanced radon concentrations to values below the national reference level. Thoron progeny concentrations (0.64 Bq m-3, on average) show correlations with year of construction and smoking behaviour. In 75 additional dwellings, a pilot study was conducted to determine the relationship between the exhalation of thoron from walls and the concentration of thoron progeny in the room. Thoron exhalation values exceeding the median value of 2.2 × 10-2 Bq m-2 s-1 by a factor 10 or more were found frequently, but enhanced concentrations of thoron progeny were measured only occasionally. Under very unfavourable conditions, however, for instance if phosphogypsum is applied as finishing material on all walls and ceilings in the house, strongly elevated thoron progeny concentrations may occur. This survey yielded a maximum recording of 13.3 Bq m-3. There is no reason to expect that such levels are specific to the Netherlands, indicating that in other regions with low radon levels, thoron may be a more important contributor to the population dose as well.