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Biomedical subjects

N D Priest

Publications and source records attributed to N D Priest.

36 records · Page 2Linked to original sources

The prediction of the relative toxicities of radium 224 and of radium 226 in the bones of mice using Monte Carlo techniques.

Toxicity studies using rodents have shown that the long-lived radium isotope radium 226 is about six times less toxic per unit of absorbed radiation dose to the skeleton than the short-lived isotope radium 224 with respect to the production of osteosarcoma. This difference in toxicity has been attributed to differences in the distribution of these isotopes. It has been suggested that 224Ra is more toxic than 226Ra because it decays on bone surfaces rather than within the volume of the bone mineral. However, in rodents many bone structures are small compared with the track length of the alpha particles and this explanation may be inadequate to explain the magnitude of the observed effect. Consequently, Monte Carlo calculations have been made to test the validity of the distribution-difference hypothesis. The results indicate that, for bone structures the size of those in mice, less than half of the observed difference in toxicity can be explained by considerations of the distribution of these radionuclides with respect to bone surfaces. Instead, it is suggested that the greater irradiation of trabecular than of cortical bone that is a characteristic of 224Ra is responsible for its enhanced toxicity.

Animals↗

Pattern of uptake of americium-241 by the rat skeleton and its subsequent redistribution and retention: implications for human dosimetry and toxicology.

The distribution and retention of intravenously injected 241Am in the skeleton of the female rat has been investigated using autoradiographic and radiochemical techniques. The studies were designed to assess the dosimetric and toxicologic implications of an 241Am intake by man. They showed that in the rat approximately one third of the intravenously injected 241Am was deposited in the skeleton where it appeared to be retained with a long biological half-time. The studies also showed: 1 241Am is initially deposited onto all types of bone surface including endosteal surfaces, periosteal surfaces and those of the vascular canals within cortical bone, but seems to be preferentially deposited onto those that are resorbing, 2 Bone accretion results in the burial of surface deposits of 241Am, 3 Bone resorption causes the removal of 241Am from surfaces, 4 Resorbed 241Am is retained by phagocytic cells (probably macrophages) in the bone marrow, 5 The transfer of 241Am from the phagocytic cells in the marrow to adjacent bone surfaces seems to occur, (local recycling). 6 The possibility that some of the 241Am removed from the bone surfaces enters the blood and is redeposited in bone, (systemic recycling) cannot be dismissed. These results show that 241Am deposition and redistribution in bone shares many characteristics with other 'bone surface-seeking radionuclides' typified by 239Pu. Consequently, it is suggested that a similar model to that used to calculate annual limits of intake for 239Pu in man would be suitable for the calculation of corresponding values for the 241Am isotopes.

Americium↗

Autoradiographic studies of the distribution of radium-226 in rat bone: their implications for human radiation dosimetry and toxicity.

A solution containing 226Ra chloride was injected into young female rats via the saphenous vein. Subsequently, the distribution and retention of the 226Ra in the skeleton was studied. The results show that: 226Ra is initially deposited in the rat femur as a volume deposit and is fairly evenly distributed throughout the bone matrix. Much of the 226Ra initially deposited in the skeleton is lost within a few days of its administration. During the first week 226Ra gradually accumulates at sites of bone deposition including accreting surfaces. Subsequent bone growth results in the burial of contaminated bone surfaces and Following bone resorption some of the 226Ra released from individual bones is recycled systemically so that all skeletal components tend towards a uniform 226Ra concentration per unit of bone mineral. Of the two models conventionally used for radiation dosimetry purposes, the results reported here for rats suggest that though neither is ideal, the volume distribution model is preferable to the surface model at all times after the uptake of radium by the skeleton.

Animals↗

The release of plutonium from macrophages in rats: the effect of changes in iron status.

Female rats were used to study the loss of plutonium from hepatic and splenic macrophages. The plutonium was administered intravenously either as a "soluble" [Pu] ferric hydroxide colloid or as an "insoluble" plutonium dioxide suspension. The "soluble" plutonium was lost much more rapidly from the liver than the "insoluble" plutonium. If the iron status of the rats was altered, shortly after the injection of the [Pu] ferric hydroxide colloid, either by the removal of blood or by the injection of colloidal iron, the rate of plutonium loss from the liver was changed. The plutonium was retained longer in those animals with excess storage iron than in those with depleted circulatory iron. These results are taken to indicate that iron and plutonium share common pathways of metabolism in macrophages.

Animals↗

Uranium in bone: metabolic and autoradiographic studies in the rat.

The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

Animals↗

Uptake and loss of plutonium from osteoclasts and macrophages in the mandibular condyle of the rat.

Female rats were used to study the kinetics of plutonium transfer from the bone surfaces of the mandibular condyle to osteoclasts and macrophages. This study was made using autoradiographs prepared from plastic sections of the mineralized bones of animals which had been injected with 241 Pu citrate. Measurements of the concentration of plutonium in the osteoclasts and macrophages at different times after the injection of plutonium showed that plutonium was concentrated by osteoclasts from bone surfaces and was retained with a half-time of approximately 70 h. Subsequently, plutonium appeared to be transferred to macrophages. The results showed that plutonium was unlikely to be accumulated by macrophages as a result of their participation in bone resorption.

Animals↗

241Plutonium deposition and redistribution in the rat rib.

Using the techniques of 241plutonium autoradiography and plutonium alpha-autoradiography the distribution of intravenously injected plutonium in the rat rib has been investigated, at times up to 4 months after injection. The results showed that at some time plutonium either became buried in the bone cortex or was resorbed. Plutonium which was resorbed was found in osteoclasts and macrophages. Subsequently, much of the resorbed plutonium was redeposited. The dosimetric implications of the results are discussed.

Alpha Particles↗

The calculation of annual limits of intake for plutonium-239 in man using a bone model which allows for plutonium burial and recycling.

Values of the annual limit of intake (ALI) for plutonium-239 in man have been calculated using committed dose equivalent limits as recommended by ICRP in Publication 26. The calculations were made using a multicompartment bone model which allows for plutonium burial and recycling in the skeleton. In one skeletal compartment, the growing surfaces of cortical bone, it is assumed that plutonium deposits are retained and are not subject to resorption or recycling. In the trabecular bone compartment plutonium is taken to be resorbed with either subsequent redeposition onto bone surfaces or retention in the bone marrow. ALIs for plutonium-239 have been calculated assuming a range of rates of bone accretion (0-32 micron yr-1), different amounts of plutonium retained in the marrow (0-60%) and a 20%, 45% or 70% deposition of plutonium in the skeleton from the blood. The calculations made using this bone model suggest that 750 Bq (20 nCi) is an appropriate ALI for the inhalation of class W and class Y plutonium compounds and that 830 kBq and 5 MBq (23 muCi and 136 muCi) are the appropriate ALIs for the ingestion of soluble and insoluble forms of plutonium respectively.

Administration, Oral↗

The uptake and redistribution of 241pu within the gonads.

Male and female hamsters and a female rabbit were injected with 241Pu citrate. The hamsters were killed serially at 15 min, 2 hours, 1 day and 10 days after injection, and the rabbit 1 week after injection. The gonads were examined for 241Pu by tissue-section autoradiography. Soon after injection the plutonium was concentrated by the contents of atretic Graafian follicles and by thecal rings in the ovary, but was found to be dispersed throughout the testes. It is suggested that the disperse distribution in the testes which is only seen soon after injection may be an artefact of tissue processing. One day after injection, plutonium was accumulated by macrophages in both the follicles of the ovary and in the interstitial tissue of the testes. Macrophages containing plutonium later migrated away from the aretic ovarian follicles towards the ovarian medulla. This pattern of distribution and redistribution in the ovary is regarded as likely to lower the effective dose from a-emitting plutonium isotopes to the viable oocytes. No migration of macrophages was seen in the testes. Histochemical staining methods revealed the presence of acid protoglycans, including chondroitin sulphate, and glycoproteins at the sites of plutonium concentration in the ovary. These molecules are regarded as likely receptor sites for plutonium. In the testes no acidic carbohydrates were found, and it is suggested that the initial binding site for plutonium may be a compound lipid. This was deduced from the apparent inability of the interstitial tissue of the testes to bind plutonium in situ.

Animals↗

The distribution of plutonium-214 in rodents.

Plutonium-214 citrate solution at pH 6-5 was injected intravenously or intra-peritoneally into hamsters and rats at a dose of 50 MBq kg-1 (1-35 mCi kg-1). The animals were killed 1 day or 1 week later, and tissues were removed for autoradiography and radiochemical analysis. Plutonium-241 was distributed in rats in the same way as plutonium-239, and is a suitable isotope for high-resolution tissue-section autoradiography. Plutonium deposits in cells consisted of a nuclear and a cytoplasmic component. In the hamster kidney cells, the amount associated with the nucleus was about 55 per cent of the total cellular plutonium at 24 hours after injection. Six days later, it was only about 30 per cent. Plutonium deposits were also characterized in hepatocytes, in the interstitial cells of the testes, in the cells of ovarian follicles, in chondrocytes and in bone cells, including osteoblasts and osteocytes. In bone there appeared to be both an extracellular and intracellular deposit. No evidence was found of substantial incorporation of plutonium into the mineral phase of bone.

Adrenal Glands↗

Plutonium in bone: a high resolution autoradiographic study using plutonium-241.

Plutonium-241 citrate solution at pH 6-5 was injected intravenously into hamsters and an adult rabbit at a dose of 10 kBq g-1 (260 nCi g-1). The hamsters were killed serially at 15 min, 2 hours, 1 day, 10 days, 1 month and 6 months after injection and the rabbit at 1 week. Their knee-joints or femora were examined for plutonium-241 by autoradiography. Few differences were found between the pattern of plutonium distribution in the hamsters and the rabbit. The results showed that although plutonium is initially distributed on bone surfaces, at long periods after injection it becomes deposited throughout the bone matrix. Plutonium uptake by cells in resorbing areas of periosteum, in active osteoblasts, and in chondrocytes in regions of cartilage mineralization was rapid. Plutonium concentrated more slowly on the resting bone surfaces and at sites of low metabolic activity. In addition, some unlabelled sections of skeletal tissues were immersed in a plutonium-241 citrate solution. When autoradiographed, it was found that plutonium was bound by cell nuclei, tooth enamel matrix, dentine, predentine and bone matrix. Plutonium binding to cartilage matrix was weak. The results are discussed with reference to the literature, and a model is proposed to explain the distribution pattern and fate of plutonium deposits in bone.

Animals↗

Source-term characterisation and solid speciation of plutonium at the Semipalatinsk NTS, Kazakhstan.

New data on the concentrations of key fission/activation products and transuranium nuclides in samples of soil and water from the Semipalatinsk Nuclear Test Site are presented and interpreted. Sampling was carried out at Ground Zero, Lake Balapan, the Tel'kem craters and reference locations within the test site boundary well removed from localised sources. Radionuclide ratios have been used to characterise the source term(s) at each of these sites. The geochemical partitioning of plutonium has also been examined and it is shown that the bulk of the plutonium contamination at most of the sites examined is in a highly refractory, non-labile form.

Journal Article↗