The analysis is most relevant to the question of practical threshold and will be discussed again in that context. The complete absence of other, less-frequent types of naturally occurring carcinoma that represent 16% of the carcinomas of specific cell type in the SEER52 study and 39% of the carcinomas in the review by Batsakis and Sciubba4 provides further evidence for perturbation of the distribution of carcinoma types by alpha radiation. The principal factors that have been considered are the nonuniformity of deposition within bone and its implications for cancer induction and the implications for fibrotic tissue adjacent to bone surfaces. Carcinomas of the paranasal sinuses and mastoid air cells may invade the cranial nerves, causing problems with vision or hearing3,23 prior to diagnosis. Rowland et al.66 plotted and tabulated the appearance times of carcinomas for five different dosage groups. s. The analysis also yields good fits to the data. In simple terms, the main issue has been linear or nonlinear, threshold or nonthreshold. The higher values of the ratios were associated with shorter exposure times, usually the order of a year or less. Autoradiographic studies37 of alkaline earth uptake by bone soon after the alkaline earth was injected into animals revealed the existence of two distinct compartments in bone (see Figure 4-3), a short-term compartment associated with surface deposition, and a long-term compartment associated with volume deposition. 35, A proportional hazards analysis of bone sarcoma rates in German radium-224 patients, Introduction to Stochastic Processes in Biostatistics, Development and Anatomy of the Nasal Accessory Sinuses in Man, The Nose: Upper Airway Physiology and the Atmospheric Environment, Radium poisoning; a review of present knowledge, The effect of skeletally deposited alpha-ray emitters in man. The mean and standard deviation in appearance times for persons first injected at ages less than 21 are 10.4 5.1 yr and for persons exposed at age 21 and above, the mean and standard deviation are 11.6 5.2 yr.46 In contrast, tumors induced by 226,228 Ra have appeared as long as 63 yr after first exposure.1 The average and standard deviation of tumor appearance times for female radium-dial workers for whom there had been a measurement of radium content in the body, was reported as 27 14 yr; and for persons who received radium as a therapeutic agent, the average and standard deviation in appearance times were 29 8 yr.69. Schlenker, R. A., and J. H. Marshall. Delayed Effects of Bone-Seeking Radionuclides, Radiogenic effects in man of long-term skeletal alpha-irradiation, ber die Beziehungen der Grossenvariationen der Highmorshohlen sum individuellen Schadelbau und deren praktische Bedeutung fr die Therapie der Kieferhohleneiterungen, Hazard plotting and estimates for the tumor rate and the tumor growth time for radiogenic osteosarcomas in man, Radiological and Environmental Research Division Annual Report, Quantitative histology of the mucous membrane of the accessory nasal sinuses and mastoid cavities, Ophthalmologic aspects of carcinoma of the sphenoid sinus induced by radium poisoning, Histologic studies of the normal mucosa in the middle ear, mastoid cavities and eustachian tube, The relative hazards of strontium 90 and radium-226, A note on the distribution of radium and a calculation of the radiation dose non-uniformity factor for radium-226 and strontium-90 in the femur of a luminous dial painter, Structural differences in bone matrix associated with metabolized radium, Alpha-ray dosimetry of the bone-tissue interface with application to sinus dosimetry in the radium cases, Radium-induced malignant tumors of the mastoids and paranasal sinuses, Cells at risk for the production of bone tumors in radium exposed individuals: An electron microscope study, Association of leukemia with radium groundwater contamination, Radioactive hotspots, bone growth and bone cancer: Self-burial of calcium-like hotspots, Measurements and models of skeletal metabolism, A theory of the induction of bone cancer by alpha radiation, Radial diffusion and the power function retention of alkaline earth radioisotopes in adult bone, Dose to endosteal cells and relative distribution factors for radium-224 and plutonium-239 compared to radium-226, Microscopic changes of certain anemias due to radioactivity, The occurrence of malignancy in radioactive persons, Bone sarcoma incidence vs. alpha particle dose, Epidemiological studies of German patients injected with, Bone sarcomas in patients given radium-224, The Health Effects of Plutonium and Radium, Bone sarcoma cumulative tumor rates in patients injected with, Morphology of the upper airway epithelium, Surveillance, Epidemiology, and End Results: Incidence and Mortality Data, 19731977, Cancer Mortality in the United States: 19501977, The EfFects on Populations of Exposure to Low Levels of Ionizing Radiation, Bone cancer among female radium dial workers, Mortality among women first employed before 1930 in the U.S. radium dial-painting industry, Comparative pathogenesis of radium-induced intracortical bone lesions in humans and beagles, Comparison of the carcinogenicity of radium and bone-seeking actinides, Bone cancer from radium: Canine dose response explains data for mice and humans, Lifetime bone cancer dose-response relationships in beagles and people from skeletal burdens of, Analysis of the radioactive content of tissues by alpha-track autoradiography, The risk of malignancy from internally-deposited radioisotopes, Radiation Research, Biomedical, Chemical, and Physical Perspectives, Radium in human bone: The dose in microscopic volumes of bone, The appearance times of radium-induced malignancies, Radiological Physics Division Annual Report, Dose-response relationships for female radium dial workers, Dose-response relationships for radium-induced bone sarcomas, Long-term retention of radium in female former dial workers, The embryology, development and anatomy of the nose, paranasal sinuses, nasolacrimal passageways and olfactory organ in man, Dosimetry of paranasal sinus and mastoid epithelia in radium-exposed humans, Critical Issues in Setting Radiation Dose Limits, Mucosal structure and radon in head carcinoma dosimetry, The distribution of radium and plutonium in human bone, Microscopic distribution of Ra-226 in the bones of radium cases: A comparison between diffuse and average Ra-226 concentrations, The Health Effect of Plutonium and Radium, Thicknesses of the deposits of plutonium at bone surfaces in the beagle, High concentrations of Ra-226 and Am-241 at human bone surfaces: Implications for the ICRP 30 Bone dosimetry model, Argonne-Utah studies of Ra-224 endosteal surface dosimetry, Zur Anatomie der menschlichen Nasennebenhohlen, ber das ausmass der Mastoidpneumatiation beim Menschen, Leukemia incidence in the U.S. dial workers, Bone cancers induced by Ra-224 (ThX) in children and adults, Protraction effect on bone sarcoma induction of, Strahlenindizierte Knochentumoren nach Thorium X-Behandlung, Mortality from cancers of major sites in female radium dial workers, Skeletal location of radiation-induced and naturally occurring osteosarcomas in man and dog, Goblet cells and glands in the nose and paranasal sinuses, Biological Effects of Low-Level Radiation, Locations of Bone Sarcomas among Persons Exposed to, Relative Frequencies for Radium-Induced and Naturally Occurring Tumors by Age Group, Carcinomas of the Paranasal Sinuses and Mastoid Air Cells among Persons Exposed to, Incident Leukemia in Located Radium Workers, Cancer Incidence Rate among Persons Exposed to Different Concentrations of Radium in Drinking Water, Effect of Single Skeletal Dose of 1 rad from. i). Platinum and eosin, once thought to focus the uptake of 224Ra at sites of disease development, have been proven ineffective and are no longer used. The functional form found to provide a best fit to the data was: where /N is the cumulative incidence, and D The first case of bone sarcoma associated with 226,228Ra exposure was a tumor of the scapula reported in 1929, 2 yr after diagnosis in a woman who had earlier worked as a radium-dial painter.42 Bone tumors among children injected with 224Ra for therapeutic purposes were reported in 1962 among persons treated between 1946 and 1951.87. Occasionally, data from several studies have been analyzed by the same method, and this has helped to illuminate similarities and differences in response among 224Ra, 226Ra, and 228Ra. In a report by Finkel et al.,18 mention is made of seven cases of leukemia and aplastic anemia in a series of 293 persons, most of whom had acquired radium between 1918 and 1933. Source: International Commission on Radiological Protection (ICRP).29. These were plotted against a variety of dose variables, including absorbed dose to the skeleton from 226Ra and 228Ra, pure radium equivalent, and time-weighted absorbed dose, referred to as cumulative rad years. Before concern developed over environmental exposure, attention was devoted primarily to exposure in the workplace, where the potential exists for the accidental uptake of radium at levels known to be harmful to a significant fraction of exposed individuals. ; Volume 35, Issue 1, of Health Physics; the Supplement to Volume 44 of Health Physics; and publications of the Center for Human Radiobiology at Argonne National Laboratory, the Radioactivity Center at the Massachusetts Institute of Technology, the New Jersey Radium Research Project, the Radiobiology Laboratory at the University of California, Davis, and the Radiobiology Division at the University of Utah. Such cells could accumulate average doses in the range of 100300 rad, which is known to induce transformation in cell systems in vitro. 1982. Most of the points lie above the model curve for the first 12 days because no correction for fecal delay has been made. Also, mortality statistics as they now exist include the effect of environmental exposures to radium isotopes. Otherwise, the retention in bone is estimated by models. Rowland et al.67 performed a dose-response analysis of the carcinoma data in which the rate of tumor occurrence (carcinomas per person-year at risk) was determined as a function of radium intake. 1983. In 1977 it was estimated that only 15 people died in the United States from cancers of the auditory tube, middle ear, and mastoid air cells.53 Comparable statistics are lacking for cancers of the ethmoid, frontal, and sphenoid sinuses; but mortality, if scaled from the incidence data, would not be much greater than that caused by cancers of the auditory tube, middle ear, and mastoid air cells. i) with 95% confidence that total risk lies between I In a subsequent analysis,46 the data on juveniles and adults were merged, and an additional tumor was included for adults, bringing the number of subjects with tumors and known dose to 48. i is the total systemic intake of 226Ra plus 2.5 times the total systemic intake of 228Ra, expressed in microcuries. In later work, juvenile-adult differences have not been reported. The best-fit function, however, does contain a linear term, in contrast to the best-fit functions for the data on 226,228Ra. analysis are closely parallel and, as might be expected, lead to the same general conclusion that the response at low doses [where exp(-D) 1] is best described by a function that varies with the square of the absorbed dose. It is not known whether the similarity in appearance time distribution for the two tumor types under similar conditions of irradiation of bone marrow is due to a common origin. Parks. s, where D 1962. Their data, plus the incidence rates for these cancers for all Iowa towns with populations 1,000 to 10,000 are shown in Table 4-6. i = 0.05 Ci, the total systemic intake in 70 yr for a person drinking 2 liters of water per day at the Environmental Protection Agency's maximum contaminant level of 5 pCi/liter, the ratio is 4,700. Radium accumulates in the bones because the radium inside the blood stream is seen as calcium , so the bones absorb it which eventually leads to it breaking down the bones . s is the sum of the average skeletal doses for 226Ra and 228Ra, in rad. Restated in more modern terms, the residual range from bone volume seekers (226Ra and 228Ra) is too small for alpha particles to reach the mucosal epithelium, but the range may be great enough for bone surface seekers (228Th), whose alpha particles suffer no significant energy loss in bone mineral;78 long-range beta particles and most gamma rays emitted from adjacent bone can reach the mucosal cells, and free radon may play a role in the tumor-induction process. The mastoid air cells, like the ethmoid sinuses, are groups of interconnecting air cavities located bilaterally in the left and right temporal bones. The resultant graph of dose-response curve slopes versus years of follow-up is shown in Figure 4-6. Book, and N. J. u = 10-5 + 1.6 10-5 224Ra, 226Ra, and 228Ra all produce bone cancer in humans and animals. Practical limitations imposed by statistical variation in the outcome of experiments make the threshold-nonthreshold issue for cancer essentially unresolvable by scientific study. Harris, M. J., and R. A. Schlenker. This observation was originally made on animals given high doses where retention, at a given time after injection, was found to increase with injection level. 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. Hindmarsh, M., M. Owen, J. Vaughan, L. F. Lamerton, and F. W. Spiers. i, and when based on skeletal dose assumes that tumor rate is constant for a given dose D Spiers, F. W., H. F. Lucas, J. Rundo, and G. A. Anast. Equations for the dose rate averaged over depth, based on a simplified model of alpha-particle energy loss in tissue, were presented by Littman et al.31 for dose delivered by radium in bone and by radon and its daughters in an airspace with a rectangular cross section. Mucosal dimensions for the mastoid air cells have been less well studied. In discussing these cases, Wick and Gssner93 noted that three cases of bone cancer were within the range expected for naturally occurring tumors and also within the range expected from a linear extrapolation downward to lower doses from the Spiess et al.88 series. . Whether due to competing risks, dose protraction, or a combination, it is clear that differential radiosensitivity for this group of subjects is a hypothesis that cannot be supported. The rate for the control group was 1.14; the probability of such a difference occurring by chance alone was reported as 8 in 100. 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. There were 1,501 exposed cases and 1,556 ankylosing spondylitis controls. 1978. Radium concentrations in food and air are very low. A single function was fitted to these data to describe the change of the dose-response curve slope with the length of time over which injections were given: where y is the number of bone sarcomas per million person-rad and x is the length of the injection span, in months. 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. D Included in the above summary are four cases of chronic lymphocytic or chronic lymphatic leukemia. There is a 14% probability that the expected number of tumors lies within the shaded region, defined by allowing the parameter value in Equation 416 to vary by 2 standard errors about the mean, and a 68% probability that it lies between the solid line that is nearly coincident with the upper boundary of the shaded region and the lower solid curve. This cohort was derived from a total of about 1,400 pre-1930 radium-dial workers who had been identified as being part of the radium-dial industry of whom 1,260 had been located and were being followed up at Argonne. The first explicit description of the structure of the sinus and mastoid mucosa in the radium literature is probably that of Hasterlik,22 who described it as "thin wisps of connective tissue," overlying which "is a single layer of epithelial cells. Locations of Bone Sarcomas among Persons Exposed to 224 Ra and 226,228Ra for Whom Skeletal Dose Estimates Are Available. From this, we can conclude that much, and perhaps all, of the difference in radiosensitivity between juveniles and adults originally reported was due to the failure to take into account competing risks and loss to follow-up. It should be borne in mind that hot-spot burial only occurs to a significant degree following a single intake or in association with a series of fractions delivered at intervals longer than the time of formation of appositional growth sites, about 100 days in humans. why does radium accumulate in bones? - rybmscaffolding.co.uk Mays, C. W., T. F. Dougherty, G. N. Taylor, R. D. Lloyd, B. J. Stover, W. S. S. Jee, W. R. Christensen, J. H. Dougherty, and D. R. Atherton. The data have been normalized to the frequency for osteosarcoma and limited to the three principal radiogenic types: osteosarcoma, chondrosarcoma, and fibrosarcoma. This suggests that competing risks exert no major influence on the analysis by Raabe et al.61,62. Everyone has some exposure to radium because it is naturally occurring in the environment. Working from various radium-exposed patient data bases, several authors have observed that carcinomas of the paranasal sinuses and mastoid air cells begin to occur later than bone tumors.16,18,66,71 In the latest tabulation of tumor cases,1 the first bone tumor appeared 5 yr after first exposure, and the first carcinoma of the paranasal sinuses or mastoid air cells appeared 19 yr after first exposure; among persons for whom there was an estimate of skeletal radiation dose, the first tumors appeared at 7 and 19 yr, respectively. Incident Leukemia in Located Radium Workers. For 228Ra the dose rate from the airspace to the mastoid epithelium was about 45% of the dose rate from bone. i), based on year of entry. This duct is normally closed, and clearance By this pathway is negligible. The original cases of radium poisoning were discovered by symptom, not by random selection from a defined population. Hasterlik, R. J., L. J. Lawson, and A. J. Finkel. 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. In addition, blood vessel cells themselves sometimes convert into bone-forming osteoblasts, producing extra calcium on the spot. Postmortem skeletal retention has been studied in animals and in the remains of a few humans with known injection levels. In the data analyses that lead to these equations, a 10-yr latent period is assumed for carcinoma induction. i between 0.5 and 100 Ci. The ethmoid sinuses form several groups of interconnecting air cells, on either side of the midline, that vary in number and size between individuals.92 The sinus surfaces are lined with a mucous membrane that is contiguous with the nasal mucosa and consists of a connective tissue layer attached to bone along its lower margin and to a layer of epithelium along its upper margin. Two cases, by implication, might be considered significant. provided an interesting and informative commentary on the background and misapplications of the linear nonthreshold hypothesis.17. why does radium accumulate in bones? It is clear, therefore, that a nonzero function could be fitted to these data but would have numerical values substantially less than 28%. Higher doses of radium have been shown to cause effects on the blood (anemia), eyes (cataracts), teeth (broken teeth), and bones (reduced bone growth). They also presented an equation for depth dose from radon and its daughters in the airspace for the case of a well-ventilated sinus, in which the radon concentration was equal to the radon concentration in exhaled breath. The third analysis was carried out by Raabe et. Radiation Safety Flashcards | Quizlet For 222Rn (whose half-life is very long compared with the time required for untrapped atoms within the body to diffuse into the blood supply), this rapid diffusion results in a major reduction of the radiation dose to tissues. Health Risks of Radon and Other Internally Deposited Alpha-Emitters: Beir IV, The bone-cancer risk appears to have been completely expressed in the populations from the 1940s exposed to, The committee recommends that the follow-up studies of the patients exposed to lower doses of. Mygind, N., M. Pedersen, and M. H. Nielsen. The data are subdivided into three groups based on the 226Ra intake. No firm conclusions about the constancy or nonconstancy of tumor rate should be drawn from this dose-response analysis. The best fit of response against systemic intake was obtained for the functional form I = C + D, obtained from Equation 4-21 by setting = = 0. Table 4-7 illustrates the effect, assuming that one million U.S. white males receive an excess skeletal dose of 1 rad from 224Ra at age 40. Schlenker74 examined the uncertainties in risk estimates for bone tumor induction at low intakes and found it to be much greater than would be determined from the standard deviations in fitted risk coefficients. Studies of Radium in Human Bone | Radiology The probability of such a difference occurring by chance was 51%. demonstrated an increase of median tumor appearance time with decreasing average skeletal dose rate for a subset of radium-induced bone tumors in humans61 and for bone tumors induced in experimental animals by a variety of radionuclides.60 The validity of the analysis of mouse data has been challenged,62 but not the analysis of human and dog data. why does radium accumulate in bones? - paginaswebconcordia.com As a consequence, many sources of water contain small quantities of radium or radon. Rowland, R. E., and J. H. Marshall. No maxillary sinus carcinomas have occurred, but 69% of the tumors have occurred in the mastoids. The 3.62-day half-life of 224Ra results in a prompt, short-lived pulse of alpha radiation; in the case of the German citizens injected with this radium isotope, this pulse of radiation was extended by repeated injections. 1978. All other functional forms gave acceptable fits. 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. analysis, 226Ra and 228Ra dose contributions were weighted equally; in Rowland et al. Radium-induced carcinomas in the temporal bone are always assigned to the mastoid air cells, but the petrous air cells cannot be logically excluded as a site of origin. A person who drinks two liters of water containing 5 . The majority of the leukemias were acute myeloid leukemias. Radiogenic tumors in the radium and mesothorium cases studied at M.I.T. 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. In the case of the longer-half-life radium isotopes, the interpretation of the cancer response in terms of estimated dose is less clear. These results are in marked contrast to those of Kolenkow30 and Littman et al.31 Under Schlenker's73 assumptions, the airspace is the predominant source of dose, with the exception noted, whether or not the airspace is ventilated. Once radium-223 reaches bone, it emits alpha-particle radiation, which induces double stranded breaks in DNA, causing a local cytotoxic effect [ 6, 8 ]. This is an instance in which an extrapolation of animal data to humans has played an important role. 2 for D Radium and Strontium are known to accumulate in bones. Why does our During the first few days after intake, radium concentrates heavily on bone surfaces and then gradually shifts its primary deposition site to bone volume. He emphasized that current recommendations of the ICRP make no clear distinction between the locations of epithelial and endosteal cells and leave the impression that both cell types lie within 10 m of the bone surface; this leads to large overestimates of the dose to epithelial cells from bone. The most likely explanation is that tissue damage to the skeleton, at high doses, alters the retention pattern, primarily through the reduction in skeletal blood flow that results from the death of capillaries and other small vessels and through the inhibition of bone remodeling, a process known to be important for the release of radium from bone. Based on their treatment of the data, Mays et al.49 made the following observation: ''We have fit a variety of dose-response relationships through our follow-up data, including linear (y = ax), linear multiplied by a protraction factor, dose-squared exponential (y = ax The cause of paranasal sinus and mastoid air cell carcinomas has been the subject of comment since the first published report,43 when it was postulated that they arise ''. This method of selection, therefore, made such cases of questionable suitability for inclusion in data analyses designed to determine the probability of tumor induction in an unbiased fashion. ." These constitute about 85% of the subjects with bone sarcoma on which the most recent analyses have been based. This yielded a dose rate of 0.0039 rad/day for humans and a cumulative dose of 80 rads to the skeleton.61. Some of these complications, such as osteopenia, are reversible and severity is dose dependent. Since it is the bombardment of target tissues and not the absorption of energy by mineral bone that confers risk, the apparent carcinogenic potency of these three isotopes differs markedly when expressed as a function of mean skeletal absorbed dose, which is a common way of presenting the data. why does radium accumulate in bones? - albakricorp.com Adults and juveniles were treated separately. In the case of leukemia, the issue is not as clear. Insufficiency fractures are a common complication after radiation therapy and generally affect those bones under most physiologic stress and with the . This is what your body does with all radioactive elements and he The intense deposition in haversian systems and other units of bone formation (Figure 4-3) that were undergoing mineralization at times of high radium specific activity in blood are called hot spots and have been studied quantitatively by several authors.2528,65,77.
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