why does radium accumulate in bones?

The ratios of maximum to average lay in the range 837. The distributions of histologic types for the 47 subjects exposed to 224Ra with bone sarcoma and a skeletal dose estimate are 39 osteosarcomas, 1 fibrosarcoma, 1 pleomorphic sarcoma, 4 chondrosarcomas, 1 osteolytic sarcoma, and 3 bone sarcomas of unspecified type. However, the change was not so great as to alter the basic conclusion that the data have too little statistical strength to distinguish between various mathematical expressions for the dose-response curve. No maxillary sinus carcinomas have occurred, but 69% of the tumors have occurred in the mastoids. D This suggests that competing risks exert no major influence on the analysis by Raabe et al.61,62. It is striking, however, that the graph for radium in humans61,62 lies parallel to the graphs for all long-lived nuclides in dogs,60 where death from bone tumor tends to occur earlier than death from other causes. Unless bone cancer induced by 226Ra and 228Ra is a pure, single-hit phenomenon, some interaction of dose increments is expected, although perhaps it is a less strong interaction than is consistent with squaring the total accumulated intake when intake is continuous. Posted at 20:22h in disney monologues, 2 minutes by what happened to the other winter soldiers le bossu de notre dame paroles infernal Likes The total thickness of the mucosa, based on the results of various investigators, ranges from 0.05 to 1.0 mm for the maxillary sinuses, 0.07 to 0.7 mm for the frontal sinuses, 0.08 to 0.8 mm for the ethmoid sinuses, and 0.07 to 0.7 for the sphenoid sinuses. This type of analysis updates the one originally conducted for this group of subjects in which juvenile radiosensitivity was reported to be a factor of 2 higher than adult radiosensitivity. Cumulative incidence, computed as the product of survival probabilities in the life table,10 was used as the measure of response with errors based on approximations by Stehney. Carcinomas of the frontal sinus and the tympanic bulla, a portion of the skull comparable to the mastoid region in humans, have appeared in beagles injected with radium isotopes and actinides. For the 27 subjects for whom radium body burden information was available, they estimated that, for airspace thicknesses of 0.5 to 2 cm, the dose from radon and its daughters averaged over a 50-m-thick mucous membrane would be 2 to 5% of the average dose from 226Ra in bone. The heavy curve represents the new model. Relative Frequencies for Radium-Induced and Naturally Occurring Tumors by Age Group. The authors concluded that bone tumors most likely arise from cells that are separated from the bone surface by fibrotic tissue and that have invaded the area at long times after the radium was acquired. The question remained open, however, whether the health effects were threshold phenomena that would not occur below certain exposure or dose levels, or whether the risk would continue at some nonzero level until the exposure was removed altogether. Research should continue on the cells at risk for bone-cancer induction, on cell behavior over time, including where the cells are located in the radiation field at various stages of their life cycles, on tissue modifications which may reduce the radiation dose to the cells, and on the time behavior and distribution of radioactivity in bone. This is an instance in which an extrapolation of animal data to humans has played an important role. In this enlarged study, three cases of leukemia were recorded in the pre-1930 population, which yielded a standard mortality ratio of 73. Argonne, Ill.: At this time, it is clear that it is not a primary consequence of radium deposited in human bones. Lyman et al.35 do not claim, however, to have shown a causal relationship between leukemia incidence and radium contamination. s is 226Ra skeletal dose. There is little evidence for an age or sex dependence of the cancer risk from radium isotopes, provided that the age dependence of dose that accompanies changes in body and tissue masses is taken into account. By measuring the radium content of 50 private wells in 27 selected counties, the counties were divided into 10 low-exposure and 17 high-exposure groups. The outcome of the analyses of Rowland and colleagues was the same whether intake or average skeletal dose was employed, and for comparison with the work of Evans and Mays and their coworkers, analyses based on average skeletal dose will be used for illustration. Autoradiograph of bone from the distal left femur of a former radium-dial painter showing hotspots (black areas) and diffuse radioactivity (gray areas). In the case of the longer-half-life radium isotopes, the interpretation of the cancer response in terms of estimated dose is less clear. With the present state of knowledge, a single dose-response relationship for the whole population according to isotope provides as much accuracy as possible. Shifting to a different algorithm for dose calculation would, at a minimum, require demonstration that the new algorithm gives the same numerical values for dose as the Spiess and Mays85 algorithm for subjects of the same age and sex. The excess death rate due to bone cancer for t > 5 yr is computed from: Effect of Single Skeletal Dose of 1 rad from 224Ra Received by 1,000,000 U.S. White Males at Age 40. The intersection of the line with the appearance time axis provides an estimate of the minimum appearance time. The distribution of histologic types for radium-induced tumors is compared in Table 4-2 with that reported for naturally occurring bone tumors.11 The data have been divided into two groups according to age of record for the tumor. The analysis is most relevant to the question of practical threshold and will be discussed again in that context. For the sinuses alone, the distribution of types is 40% epidermoid, 40% mucoepidermoid, and 20% adenocarcinoma, compared with 37, 0, and 24%, respectively, of naturally occurring carcinomas in the ethmoid, frontal, and sphenoid sinuses.4 Among all microscopically confirmed carcinomas with known specific cell type in the nasal cavities, sinuses and ear listed in the National Cancer Institute SEER report,52 75% were epidermoid, 1.6% were mucoepidermoid, and 7% were adenocarcinoma. Taking the former choice, it is implied that the doses given at different times interact; with the latter choice it is implied that the doses act independently of one another. Cancer Incidence Rate among Persons Exposed to Different Concentrations of Radium in Drinking Water. Practical limitations imposed by statistical variation in the outcome of experiments make the threshold-nonthreshold issue for cancer essentially unresolvable by scientific study. i This study was aimed at the role, if any, of trihalomethanes resulting from the disinfection of water by chlorination. Finkel et al.18 concluded that the appearance of one case of CML in 250 dial workers, with about 40 yr of follow-up time, would have been above that which was expected. The advantage of using a tabular form for the calculation of the effect of radiation is that it provides a general procedure that can be applied to more complex problems than the one illustrated above. These cells are within 3080 m of endosteal bone surfaces, defined here as the surfaces bordering the bone-bone marrow interface and the surfaces of the forming and resting haversian canals. i) with 95% confidence that total risk lies between I Marshall36 showed that bone apposition during the period of hot-spot formation, following a single intake of radium, would gradually reduce the dose rate to adjacent bone surface tissues far below the maximum for the hot spot and concluded that the accumulated dose from a hot spot would be no more than a few times the dose from the diffuse component.37 Later, Marshall and Groer38 stated that most hot spots are buried by continuing appositional bone growth and do not deliver much of their dose to endosteal cells that may lie within the alpha-particle range. This, plus the high level of cell death that would occur in the vicinity of forming hot spots relative to that of cell death in the vicinity of diffuse radioactivity and the increase of diffuse concentration relative to hot-spot concentration that occurs during periods of prolonged exposure led them to postulate that it is the endosteal dose from the diffuse radioactivity that is the predominant cause of osteosarcoma induction. However, at lower radium intakes, such as those experienced by the British luminizers and the bulk of the U.S. radium-dial workers, incorporated 226Ra does not appear to give rise to leukemia. In a review of the papers published in the United States on radium toxicity, and including three cases of radium exposure in Great Britain, Loutit34 made a strong case "that malignant transformation in the lymphomyeloid complex should be added to the accepted malignancies of bone and cranial epithelium as limiting hazards from retention of radium." Among these individuals the minimum observed time to osteosarcoma appearance was 7 yr from first exposure. why does radium accumulate in bones? that contains an exponential factor. Evans et al.17 suggested an increase of median tumor appearance time with decreasing dose based on observations of tumors in a group of radium-dial painters, radium chemists, and persons who had received or used radium for medicinal purposes. 's analysis, the 228Ra dose was given a weight 1.5 times that of 226Ra. Parks. Sarcomas of the bones and joints comprise only 0.24% of microscopically confirmed malignancies reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.52 The chance of contracting bone sarcoma during a lifetime is less than 0.1%. There were 11 bone marrow failures in the exposed group, and only 4 in the control group. The majority of the leukemias were acute myeloid leukemias. This chapter focuses on bone cancer and cancer of the paranasal sinuses and mastoid air cells because these effects are known to be associated with 224Ra or 226,228Ra and are thought to be nonthreshold phenomena. An approximate approach would be to take the population as a function of age and exposure and apply the dose-response relationship to each age group, taking into account the projected survival for that age group in the coming years. Thus, the model and the Rowland et al. When these ducts are open, clearance is almost exclusively through them. When the average exposure period is several hundred days, as it was for humans exposed to 226,228Ra, there will be only a minor reduction of hot-spot dose rate because the blood level is maintained at a high average level for the whole period of formation of most hot spots.67 Autoradiographs from radium cases with extended exposures such as those published by Rowland and Marshall65 bear this out and form a sharp contrast to autoradiographs of animal bone following single injection36 on which the model of hot-spot burial was based. There is no assurance that women exposed at a greater age or that men would have yielded the same results. When the model is used for radium, careful attention should be paid to the constraints placed on the model by data on radium retention in human soft tissues.74 Because of the mathematical complexity of the retention functions, some investigators have fitted simpler functions to the ICRP model. The relative frequencies for fibrosarcomas induced by 224Ra and 226,228 Ra are also different, as are the relative frequencies for chondrosarcomas induced by 226,228Ra and naturally occurring chondrosarcomas. Leukemias induced by prolonged irradiation from Thorotrast (see Chapter 5) have appeared from 5 to more than 40 yr after injection, similar to the broad distribution of appearance times associated with the prolonged irradiation with 226,228Ra. None of these findings are in agreement with the long-term studies of higher levels of radium in the radium-dial workers. provided an interesting and informative commentary on the background and misapplications of the linear nonthreshold hypothesis.17. where 3 10-5 is the natural risk adapted here. PDF Radium-226 (226Ra) - Washington State Department of Health Presumably, if dose protraction were taken into account by the life-table analysis, the difference between juveniles and adults would vanish. This work allows one to specify a central value for the risk, based on the best-fit function and a confidence range based on the envelopes. Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. This argues for the interaction of doses and in the extreme case for squaring the cumulative dose. The decay products of radium, except radon, are atoms of solid materials. Comparable examples can be given for each expression of Rowland et al. In addition to the primary radiationalpha, beta, or bothindicated in the figures, most isotopes emit other radiation such as x rays, gamma rays, internal conversion electrons, and Auger electrons. Bean, J. Schlenker, R. A., and J. H. Marshall. For the functions of Rowland et al. Knowing the death rate as a function of time for each starting age then allows the impact of radiation exposure to be calculated for each age group and to be summed for the whole population. a. As of December 1982, the average followup time was 16 yr for patients injected after 1951 with lower doses of 224Ra for the treatment of ankylosing spondylitis.93 Of 1,426 patients who had been traced, the vital status for 1,095 of them was known. This study examined a cohort of 634 women who had been identified by means of employment lists or equivalent documents. On the basis of minimum and median appearance times, they concluded that the appearance times do not change with dose. How are people exposed to radium? Lyman, G. H., C. G. Lyman, and W. Johnson. The complexity of the problem is illustrated by their findings for Chicago. Based on Kolenkow's work,30 Evans et al.16 reported a cumulative dose of 82,000 rad to the mucous membrane at a depth of 10 m for the subject with carcinoma. All of these cases occurred among 293 women employed in Illinois; none were recorded among the employees from radium-dial plants in other states. The time course for development of fibrosis and whether it is a threshold phenomenon that occurs only at higher doses are unknown. It is absorbed from the soil by plants and passed up the food chain to humans. Littman et al.31 have presented a list of symptoms in tabular form gleaned from a study of the medical records of 32 subjects who developed carcinoma of the paranasal sinuses or mastoid air cells following exposure to 226,228Ra. The loss is more rapid from soft than hard tissues, so there is a gradual shift in the distribution of body radium toward hard tissue, and ultimately, bone becomes the principal repository for radium in the body. He also described the development of leukopenia and anemia, which appeared resistant to treatment. 2)exp(-1.1 10-3 1959. International Commission on Radiological Protection (ICRP). Were it not for the fact that these cancers were not seen at radium intakes hundreds to thousands of times greater in the radium-dial painter studies, they might throw suspicion on radium. Radon is gaseous at room temperature and is not chemically reactive to any important degree. It peaks about 5 yr after exposure following the passage of a minimum latent period. As dose diminishes below the levels that have been observed to induce bone cancer, cell survival in the vicinity of hot spots increases, thus increasing the importance of hot spots to the possible induction of bone cancer at lower doses. Source: Mays and Spiess. why does radium accumulate in bones? 1972. The results are shown in Figure 4-8. The first attempts at quantitative dosimetry were those of Kolenkow30 who presented a detailed discussion of frontal sinus dosimetry for two subjects, one with and one without frontal sinus carcinoma. Incident Leukemia in Located Radium Workers. Most of the points lie above the model curve for the first 12 days because no correction for fecal delay has (more). Evans et al. The shaded region emphasizes that standard errors obtained by least-square fitting underestimate the uncertainty in risk at low doses. Pool, R. R., J. P. Morgan, N. J. The quantitative impact of cell location on dosimetry was emphasized by Schlenker75 who focused attention on the relative importance of dose from radon and its daughters in the airspaces compared to dose from radium and its daughters in bone. It shows no signs of significant secretory activity but is always moist. Whole-body radium retention in humans. Spiers, F. W., H. F. Lucas, J. Rundo, and G. A. Anast. Radium has been used commercially in luminous paints for watch and instrument dials and for other luminized objects. Concurrently, Mays and Lloyd44 analyzed the data on bone tumor induction by using Evans' measures of tumor incidence and dosage without correction for selection bias and presented the results in a graphic form that leaves a strong visual impression of linearity, but which, when subjected to statistical analysis, is shown to be nonlinear with high probability. Call (225) 687-7590 or what can i bring on a cruise royal caribbean today! Carcinomas of the Paranasal Sinuses and Mastoid Air Cells among Persons Exposed to 226,228Ra and Currently Under Study at Argonne National Laboratory. Malignancies of the auditory tube, middle ear, and mastoid air cells (ICD 160.1) make up only 0.0085% of all malignancies reported by the National Cancer Institute's SEER program.52 Those of the ethmoid (ICD 160.3), frontal (ICD 160.4), and sphenoid (ICD 160.5) sinuses together make up 0.02% of all malignancies, or if the nonspecific classifications, other (ICD 160.8) and accessory sinus, unspecified (ICD 160.9), are added as though all tumors in these groups had occurred in the ethmoid, frontal, or sphenoid sinuses, the incidence would be increased only to 0.03% of all malignancies. Book, and N. J. In this way, some problems of selection bias could be avoided, because most radium-dial workers were identified by search, and coverage of the radium-dial worker groups was considered to be high. This large difference has prompted theoretical investigations of the time dependence of hotspot dose rate and speculations on the relative importance of hot-spot and diffuse components of the radioactivity distribution for tumor induction. In the context of radioactive poisoning by Radium and Strontium, it is known that they accumulate in the human skeleton and thus have a cumulative effect over time. Error bars on the points vary in size, and are all less than about 6% cumulative incidence (Figure 4-4). For five subjects on whom he had autoradiographic data for the 226Ra specific activity in bone adjacent to the mastoid air cells, the dose rate at death from 222Rn and its daughters in the airspaces exceeded the dose rate from 226Ra and its daughters in bone. With 228Ra, dose delivery is practically all from bone volume, but the ranges of the alpha particles from this decay series exceed those from the 226Ra decay series, allowing 228Ra to go deeper into the bone marrow and, possibly, to irradiate a larger number of target cells. Create a gas-permeable layer beneath the slab or flooring.. why does radium accumulate in bones? The data on human soft-tissue retention were recently reviewed.74 The rate of release from soft tissue exceeds that for the body as a whole, which is another way of stating that the proportion of total body radium that eventually resides in the skeleton increases with time. When an excess has occurred, there exist confounding variables. why does radium accumulate in bones? - s158940.gridserver.com For animals given a single injection, hot spots probably played a role similar to that played by diffuse radioactivity. Some 87 bone sarcomas have occurred in 85 persons exposed to 226,228 Ra among the 4,775 persons for whom there has been at least one determination of vital status. Since leukemia rates are not elevated in the radium-dial worker studies, where the radium exposures ranged from near zero to many orders of magnitude greater than could be attributed to drinking water, it is difficult to understand how radium accounts for the observations in this Florida study. There is evidence that 226,228Ra effects on bone occur at the histological level for doses near the limit of detectability. s, where D All other functional forms gave acceptable fits. In simple terms, the main issue has been linear or nonlinear, threshold or nonthreshold. However, it is difficult to accept this hypothesis without an explanation of the lesser number of cancers found at higher radium intakes. A total of almost 908,000 residents constituted the exposed population; the mean level of radium in their water was 4.7 pCi/liter. Since radium is present at relatively low levels in U.S. white male mortality rates for 1982 from Statistical Abstract of the United States, 106th ed., U.S. Department of Commerce, Washington, D.C., 1986. Hindmarsh, M., M. Owen, J. Vaughan, L. F. Lamerton, and F. W. Spiers. A recent examination of data on whole-body radium retention in humans revealed that the excretion rate diminished with increasing body burden.70 Absolute retention could not be studied, because the initial intake was unknown, but the data imply the existence of a dose-dependent retention similar to that observed in animals. This type of analysis was used by Evans15 in several publications, some of which employed epidemiological suitability classifications to control for case selection bias. Each isotope of radium gives rise to a series of radioactive daughter products that leads to a stable isotope of lead (Figure 4-1a and 4-1b). This ratio increases monotonically with decreasing endosteal dose, from 1.8 at 500 rad to 220 at 25 rad, which is the lower boundary of the lowest dose cohort used in Schlenker's74 analysis. Groer and Marshall20 estimated the minimum time for osteosarcoma appearance in persons exposed to high doses of 226Ra and 228Ra. Raabe et al. The same observation can be made for the function 1 - exp(-0.00003D) for the probability of tumor induction developed from the life-table analysis of Schlenker.74. Whether these effects magnify other skeletal problems is unknown, but issues such as these leave the threshold-nonthreshold question open to further investigation. 1975.

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