Leukemia in the proximity of a German boiling-water nuclear reactor: evidence of population exposure by chromosome studies and environmental radioactivity.

Exceptional elevation of children's leukemia appearing 5 years after the 1983 startup of the Krümmel nuclear power plant, accompanied by a significant increase of adult leukemia cases, led to investigations of radiation exposures of the population living near the plant. The rate of dicentric chromosomes in peripheral lymphocytes of seven parents of children with leukemia and in 14 other inhabitants near the plant was significantly elevated and indicated ongoing exposures over the years of its operation. These findings led to the hypothesis that chronic reactor leakages had occurred. This assumption is support by identification of artificial radioactivity in air, rainwater, soil and vegetation by the environmental monitoring program at the nuclear power plant. Calculations of the corresponding source terms show that emissions must have been well above authorized annual limits. Bone marrow doses supposedly result primarily through incorporation of bone-seeking beta- and alpha-emitters.


Introduction
A cluster of childhood leukemia cases was observed in the community of Elbmarsch in northern Germany in 1989 to 1991 (1-3). All five cases had been living within a distance of 5 km from the Kriimmel nuclear power plant (Kernkraftwerk Krummel [KKK]) located near the river Elbe about 35 km southeast of Hamburg. Since 1994, four additional cases were identified in the 5-km area surrounding KKK ( Figure 1). All these cases were diagnosed at 10 years of age or younger; five were very young: 1.8 to 4 years of age (Table 1). Also, one case of leukemia This paper is based on a presentation at the International Conference on Radiation and Health held 3-7 November 1996 in Beer Sheva, Israel. Abstracts of these papers were previously published in Public Health Reviews 24 (3)(4): 205-431 (1996). Manuscript received at EHP 18 April 1997; accepted 22 July 1997. in a young adult and a case of aplastic anemia in a child were diagnosed.
Between 1986 and 1995 the mean number of children up to the age of 14 living in the 5-km area surrounding KKK was about 5400 (4). According to Haaf et al. (5), the mean incidence of acute leukemia between 1980 and 1990 was 4.3 x 10-5 a-l in individuals less than 15 years of age. The expected number of leukemia cases in children in the 5-km region around KKK for the period 1990 to 1996 was 1.6; therefore, the incidence of childhood leukemia in that region was elevated by a factor of 5.6.
The Kriimmel nuclear power plant is a 1 300-mW boiling-water reactor-the largest in the world-and began operation in 1983. The nuclear research institute Gesellschaft fur Kernenergieverwertung in Schiffbau und Schiffahrt (GKSS) is located in this plant's vicinity. The GKSS was established in 1958 and operates two research reactors of S and 15 mW.
The governments of the Federal States of Lower Saxony and Schleswig-Holstein have established a board of experts to identify possible causes of the observed leukemia cluster. Potential risk factors such as X-rays, chemicals, and previous diseases of the affected families were noted and excluded from the study. None of the parents were exposed to occupational or unusual medical irradiation. One family, however, was living in a house with a mean radon concentration of 450 Bq/m3. The only common factor among the leukemia cases was their proximity to the two nuclear establishments. With respect to KKK, not only the spatial relationship of the observed leukemia cluster to the nuclear power plant is remarkable but also the temporal correspondence. The first case of malignant blood disease was diagnosed 5 years after KKK was commissioned.
A retrospective epidemiologic study by Hoffmann and Greiser (6) in 1994 showed an elevation in the incidence of leukemia in the whole population in the vicinity of KKK. For the period 1984 to 1993 there was a statistically significant elevation for males (+56%) within 5 km of the nuclear power plant. This increase was confined to the period 1989 to 1993; it began 5 years after the KKK startup. A careful investigation of the possible relationship between the cluster of leukemia cases and the local nuclear facilities appeared imperative even though the whole-body counting of inhabitants performed in 1991 produced negative results and analyses concerning the emission of long-lived fission products failed to demonstrate a consistent pattern of increased radionuclide concentrations in soil and vegetation (7). There were, however, several isolated findings of elevated radionuclide activities measured in environmental samples at various times (8).
To examine whether the population living in the vicinity of KKK was subjected to elevated exposures of ionizing radiation, analyses of dicentric chromosome aberrations in lymphocytes of the peripheral blood were conducted for a group of inhabitants of the Elbmarsch community. Analyses of data on environmental radioactivity measurements also were conducted.  Each subject completed a detailed questionnaire. Exclusion criteria were previous occupational exposures, greater-thanaverage diagnostic medical irradiation, or exposure to chemical mutagens. Smokers (those who smoked more than 10 cigarettes per day) were also excluded.
To evaluate the rate of dicentric chromosomes and centric ring chromosomes, lymphocyte cultures and slide preparations were made according to standard cell cycle controlling methods (9). Collection of metaphases was facilitated by a semiautomatic computerized system that included data management (Metasystems, Sandhausen, Germany). Only first-division metaphases with 46 centromeres were analyzed and all structural aberrations were registered. The results are given in Table 2.
Particularly noteworthy was the existence of cells with two dicentrics in the Elbmarsch group (Table 2, cases 5, 8, 10, and 12) in contrast to the control group (no cells with more than one dicentric). Additionally, there was one metaphase with six dicentrics ( Table 2, case 3). The aberrations did not follow Poisson distribution but showed a significant overdispersion (11). This was true for the entire Elbmarsch population investigated, even when the multiaberrant cell was excluded (Table 3). Although the results of the chromosome aberration analysis indicate that the population of the Elbmarsch community has been severely exposed to ionizing radiation in the past (12), extrapolation of the entire accumulated dose is not adequate because exposure conditions are not known.

Gamma Dose in the Surrounding Area
The major focus of the environmental monitoring program of KKK and GKSS is y dose rate and accumulated y dose (7,8,13,14). The annual external 'y dose is controlled by 80 thermoluminescence dosimeter(s) (TLD) distributed at different locations (13). We analyzed the results by regarding two zones: 0 to 2.5 km (a total of 11 locations excluding measurements at the KKK site) and 7.5 to 15 km (34 dosimeters). By calculating annual averages for each of the zones it was determined that there was systematic elevation of 'y exposure in the internal zone since the beginning of operation in 1983 to about 1992 ( Figure  2). In the 2 years before the KKK startup the external y doses in the two zones were statistically similar.
The difference in y exposures corresponds to a mean additional exposure of "Excluding one multiaberrant cell with six dicentrics. bOne cell contained one tricentric, which was counted as two dicentrics. clncluding one cell with two dicentrics. dStandard error of the mean.

Cesium Isotopes in Rainwater and Air
Long-lived y emitters are routinely measured in the vicinity of KKK (13,14). Concentrations in rainwater are measured periodically at three locations. Figure 3 shows 137Cs activity in precipitation at these sampling stations. The Grunhof station, which is 2.2 km downwind of KKK, has shown a decreasing but permanent elevation of isotopes 134Cs and 137Cs since 1986.
These isotopes were elevated compared to isotope incidence at other locations of the KKK monitoring program and the 137cs concentration was at least 10-fold higher than that at other measuring points in northern Germany from the third quarter of 1986 until 1993 (16). Thus, Chernobyl fallout can be excluded as a cause of such elevations. In addition, the presence of the 134Cs isotope in these samples indicates that the contaminations cannot be attributed to the fallout from nuclear weapons testing because of the short half-life of 134Cs (2.1 years).
Calculations and measurements demonstrate that the releases of radioactivity permitted by German nuclear facilities do not lead to detectable contamination in the surrounding areas (17). Therefore, findings of Cs in rainwater appear to be an indication of repeated releases of nuclides above permitted limits.
Elevated Cs emissions have been confirmed by measurements of dry fallout at different locations near KKK (13). Compared to that in other locations in Germany, the 137Cs aerosol concentration in air near the grou4nd in the vicinity of KKK was significantly elevated in different quarters in the period 1985 to 1995 (Table  4). It should be noted that these measurements were carried out by three different laboratories; therefore, repeated measurement errors can be discounted. Additionally, remarkable concentrations of 90Sr were found in 1984 and 1988, which also cannot be explained by any other sources than KKK emissions (90Sr in rainwater was not measured).

Fission and Activation Products in Soils and Green Plants
Measurements of environmental samples show elevated activities of the nuclides '37Cs and 90Sr in soil and plants since the startup of KKK (13,14). The Chernobyl accident led to only marginal increases of 90Sr in the German environment (17). Nevertheless, concentrations of this isotope rose repeatedly by several Bq/kg (dry mass) compared to the background fallout in the grass around KKK. The highest 90Sr contamination-30 Bq/kg (dry mass)-was registered in August 1987 at a location 10 km from KKK; this is more than 10-fold the normal concentration in Germany at that time (18,19).The highest concentration of 137Cs in grass (103 Bq/kg) was measured in 1988 2 km from KKK (13). This is an approximately 100-fold increase over the normal value in local vegetation (19).
The KKK environmental monitoring program does not call for nuclide-specific and continuous measurements of pure 5-and a-emitters in the controlled media except for 90Sr in the air. Measurements of short-lived y and 5-emitters are also not required. Nevertheless, there have been occasional findings of short-lived fission and activation products as well as radioactive corrosion products, none of which can be explained by the Chernobyl accident (Table 5). Only after damage to the fuel rods would these nuclides be detectable outside the plant. In these cases leakages of primary cooling water would be   accompanied by releases of Pu and other transuranium isotopes (20). In 1984 Pu isotopes were found in surface water of the Elbe River and in fish in the river (8). When the activity ratios of isotopes 238pu and 2391240Pu are compared, it is concluded that they were generated in a reactor and are not the result of weapons fallout. No Pu measurements were available after 1984. A further indication of Pu releases is in the discovery of 239Np in soil in 1993 because 239Np is a precursor of 239Pu (Table 5).

Discussion
Elevated rates of leukemia among populations in the vicinity of nuclear establishments have been found repeatedly (21)(22)(23). For example, in the case of the Pilgrim nuclear reactor in Massachusetts, a correlation between the leukemia rates in the vicinity of the plant and official information on releases of radioactivity was established and a cause-effect relationship derived (24). In western Germany, an incidence study of childhood leukemia near nuclear establishments in the former countries of the Federal Republic had negative results (25). However, with respect to populations residing in a radius of less than 5 km from a nuclear establishment and children less than 5 years of age at diagnosis, there was a 3-fold significant elevation in leukemia incidence compared to that in control regions (25).
The study by Keller and co-workers (25) was restricted to the period 1980 to 1990; therefore, most of the cases of childhood leukemia near KKK were not included. Most of these children became ill at very young ages ( Table 1). The hypothesis of radiation induction is thus supported by the well-known fact that individuals in the prenatal stage and at very young ages have a higher sensitivity to radiation. Furthermore, the predominance of illnesses among boys (Table 1) corresponds to the findings among A-bomb survivors in which the male:female ratio is 2:1 for radiationinduced cases (26); the normal ratio for such illnesses is 1.3:1 (5).
Further support for the hypothesis of radiation-induced leukemia in the Elbmarsch region has been found through investigations of the latency periods for leukemia in exposed cohorts. Children 0 to 15 years of age receiving X-ray therapy for ringworm of the scalp showed a maximum rate of leukemia about 4 years after irradiation; 50% of all cases occurred by this time (27,28). This corresponds to the distribution in the Oxford Survey of Childhood Cancers for leukemia after prenatal exposure to diagnostic X-rays (29), and to age correlations in latent cases of radiationinduced illnesses among Japanese A-bomb survivors (30).
Assuming 4 years of latency and realizing that the first appearance of childhood leukemia in the proximity of KKK was in 1990 (Table 1), a single exposure event in 0.6 "All values except the last five entries in column 3 are derived by air filter measurements and contain all results above the detection limits (13,14). Values for the last five entries of column 3 are measurements of the dry fallout by deposition, which have been converted into air concentrations. bThe data from the locations Braunschweig (northern Germany), Berlin and Freiburg (southern Germany) are taken from the annual reports on environmental radioactivity and radiation of the Federal Ministry of Environment (19). cMeasurements made by KKK. dMeasurements made by an independent second laboratory. From the medical and biological findings discussed in this paper, we conclude that the population was affected by repeated exposures for the following reasons. First, at least four of the children with leukemia were born after 1987 (Table 1). Second, the repeated exposures are indicated by the results of the chromosome aberration analysis. Dicentric chromosomes are unstable aberrations with a decline of about 40%/year (12). Therefore, backdating the measured rates of dicentric chromosomes to a single event in 1986 or earlier would yield unrealistically high original rates of exposure. Third, the elevated rate of dicentric chromosomes is similar for persons who settled in Elbmarsch both before and after 1986 ( Table 2).
Dose estimations based on the observed rate of dicentric chromosomes in Elbmarsch inhabitants are not reliable because neither the time nor the conditions surrounding the exposures are known. The findings about overdispersion of the distribution of aberrations per cell, however, give additional information about the kind of exposure. Overdispersion of dicentric chromosomes can be caused by either nonuniform or high linear energy transfer (LET) irradiation. Such distributions have been found in blood samples of persons occupationally exposed to plutonium (31), tritium (32), or uranium (33). This cannot be proven through available data or measurements for the Elbmarsch population. The overdispersion observed in the present study also is unexplainable by external y irradiation or other kinds oflow-dose low LET exposure.
The supervising ministry in Schleswig-Holstein has denied that KKK is responsible for exposing the population in the vicinity of the plant and refers to the results of the extensive y monitoring of the surrounding area. Although there is no indication of a severe overexposure to external y irradiation in that region, the supposed bone marrow dose may have been a result of incorporation of aand P-aerosols, whereas the y submersion was negligible. Scenarios that lead to such organ doses are described in connection with accidents caused by cooling water effluent (20). In addition, fuel-rod failures are a well-known problem in nuclear reactors. Because it has the largest boilingwater reactor in the world, the Kriimmel nuclear power plant is a unique installation. A recent television documentary reported severe problems encountered during construction of the pressure vessel with regard to the welding of single elements. The leukemia study researchers learned of significant leakages of cooling media from the pressurized system during almost all the years of operation (34). The quantities rose to 300 liters/hr in 1986 and increased to more than 200 liters/hr in 1993 and 1996. Further investigations will consider the relevance of these leakages by analyzing the pattern of observed nuclides in the areas surrounding KKK.