strontium-radioisotopes and Hemangiosarcoma

Bone tumours from beagles exposed by inhalation to 90SrCl2 at the Inhalation Toxicology Research Institute (ITRI), by chronic ingestion of 90Sr at the Laboratory of Energy-Related Health Research (LEHR), and by injection of 90Sr citrate at the University of Utah were analysed to determine if the bone tumour characteristics differed among the three studies. The range of average skeletal doses at which the bone tumours occurred was similar in all three studies, but differences in the skeletal distribution, histological phenotype, and time to death were observed. The differences observed were attributed to the difference in dose-rate pattern obtained in the chronic ingestion study, in contrast to the inhalation and injection studies. In general, however, the differences noted in bone tumour characteristics were subtle, and would be unlikely to make an impact on models developed to assess the risk of human exposure to 90Sr.

Topics: Administration, Inhalation; Administration, Oral; Animals; Bone Neoplasms; Dogs; Hemangiosarcoma; Injections, Intravenous; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

The commonest skeletal tumour occurring in male CBA and C3H mice injected with 7--13 muCi 90Sr (per mouse) at Harwell was diagnosed with the light microscope as haemangiosarcoma. On the other hand, Nilsson, using male CBA mice injected with similar amounts of 90Sr, recorded the predominant tumour as fibroblastic osteosarcoma. To resolve the apparent discrepancy, samples of non-osteogenic tumours induced by 90Sr at Harwell were examined with the electron microscope and their ultrastructure compared with that described for fibroblastic osteosarcoma by Nilsson. The tumours diagnosed as haemangiosarcoma at Harwell showed ultrastructural features not observed in the fibroblastic osteosarcomas. Vasoformation was marked, the vascular channels varying in shape, size and in the character of their lining cells. Some vascular channels were lined by cuboidal cells, crowded together, and surrounded by a basement membrane. Others were lined by an attenuated endothelium and often formed networks. The tumour cells showed great variation in shape, size and ultrastructure and were sometimes enclosed by a basement membrane. Thus the ultrastructure of the tumours described in this report supports the diagnosis of haemangiosarcoma, rather than fibroblastic osteosarcoma. The question of whether these haemangiosarcomas truly originate from vascular endothelium, or are mimics, is discussed.

Topics: Animals; Bone Neoplasms; Hemangiosarcoma; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Microscopy, Electron; Neoplasms, Radiation-Induced; Sarcoma, Experimental; Strontium Radioisotopes

In primary bone tumors the possibilities of bone scans are discussed. Exact differentiation between malignant and benign disease by this method is impossible. However, scanning provides important information about extent of the disease, metastases, multiplicity of benign lesions and influence of adjoining diseases to the bone. A special indication exists in cases of cerebral meningiomas and an absolute indication for searching osteoplastic metastases, e.g. in carcinomas of the breast and the prostate gland.

Topics: Bone Diseases; Bone Neoplasms; Child; Fluorine; Granuloma; Hemangiosarcoma; Humans; Male; Meningioma; Neoplasm Metastasis; Osteitis Deformans; Osteoma; Radioisotopes; Radionuclide Imaging; Sarcoma, Ewing; Strontium; Strontium Isotopes; Strontium Radioisotopes; Technetium

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.

Topics: Aging; Animals; Bone and Bones; Bone Neoplasms; Fibrosarcoma; Hemangiosarcoma; Lymphoma; Mice; Mice, Inbred A; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred Strains; Neoplasms, Radiation-Induced; Osteosarcoma; Plutonium; Radiography; Radium; Species Specificity; Strontium Radioisotopes

In a series of experiments, mainly CBA/H, but also C2H/H, mice aged 3 months were injected intraperitoneally with solutions of 90Sr Cl2, the dose per mouse varying from 7 to 20 muCi, and compared with similar mice treated with 226Ra or 239Pu, discussed elsewhere. In male mice, the commonest tumour resulting at each dose of 90Sr was non-osteogenic (angio) sarcoma, a tumour not seen after 226Ra. In females, this tumour occurred far less frequently than osteosarcoma. In CBA mice of both sexes converted to radiation chimaeras (which are sterile) and similarly treated with 90Sr, the only skeletal tumours were osteosarcomas. When only half the body of CBA mice was X-irradiated with 1000 rad and the mice given 90Sr, non-osteogenic sarcoma occurred predominantly in those mice X-irradiated in the cephalic half. The results suggest that intact testes may provide co-factors for this type of neoplasm, whereas others have shown that oestrogens facilitate murine osteosarcoma. The non-osteogenic osteosarcomas arise from damaged stromal elements in bone-marrow of selected bones. The risk to this component of bone-marrow, as well as to haematopoietic tissue, should be considered in radiation protection.

Topics: Animals; Bone Marrow; Bone Neoplasms; Female; Hemangiosarcoma; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radiography; Strontium Radioisotopes

Beta-emitting radionuclides are important constituents of isotope inventories in light water reactors and may pose an inhalation hazard to industrial workers or the general population if they are released. To study the biological effects of such potential exposures, a series of life span studies was initiated in which beagle dogs were exposed to aerosols of relatively insoluble fused clay particles containing 90Y, 91Y, 144Ce or 90Sr. Groups of dogs exposed to each radionuclide received graded initial lung burdens of radioactivity. When combined with the varied physical half-lives of the four radionuclides, this resulted in a wide variety of radiation doses and dose patterns to the lung. Deaths (greater than 640 days after exposure) were generally associated with pulmonary neoplasia in dogs that inhaled 91Y, 144Ce or 90Sr. These dogs had cumulative lung doses to death greater than 20 000 rads. Exposure to 144Ce or 90Sr with dose rates that decreased slowly induced pulmonary haemangiosarcomas. Pulmonary irradiation from 91Y, with a rapidly decreasing dose rate, resulted in pulmonary epithelial tumours. No malignant lung tumours have been seen within 1540 days after exposure to 90Y. The animals in the main studies have been observed for 1342 to 2756 days after exposure.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aerosols; Animals; Carcinoma, Squamous Cell; Cerium Radioisotopes; Dogs; Female; Fibrosarcoma; Hemangiosarcoma; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Strontium Radioisotopes; Time Factors; Yttrium Radioisotopes

In a series of related experiments to evaluate the relative toxicity of inhaled radionuclides, beagles were exposed to aerosols containing relatively soluble (chloride) or relatively insoluble (fused clay) forms of 144-Ce and 90Sr. With the solubled 144-CeCl3, significant radiation doses were delivered to the lungs, liver, and skeleton whereas, after 90-SrCl2 exposure, the radiation dose was delivered predominantly to the skeleton. In dogs exposed to 144-Ce and 90-Sr in fused clay particles, radiation doses were delivered mostly to the lungs and tracheobronchial lymph nodes. In most dogs dying within 2 years after exposure, deaths were attributable to nonneoplastic radiation-induced lesions in the target organ systems. At later times after exposure, neoplasms were the major cause of death, again occurring mostly in target organs or the adjacent tissues. Lung liver, and bone-related neoplasms, including five hepatic hemangiosarcomas, developed after 144-CeCl3 exposure. Among the bone-related sarcomas seen in dogs exposed to 144-CeC3 or 90-SrC2, the incidence of hemangiosarcomas was over 40%. Among the 20 dogs dying with pulmonary neoplasms after exposure to 144-Ce or 90Sr in fused clay particles, all had hemangiosarcomas and several also had other neoplasms. This high after exposure and differs from results in other laboratories where beagles have been exposed to both alpha and beta-emitting radionuclides.

Topics: Aerosols; Animals; Bone and Bones; Bone Neoplasms; Cesium Radioisotopes; Dogs; Hemangiosarcoma; Humans; Infant, Newborn; Liver; Liver Neoplasms; Lung; Lung Neoplasms; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Radioisotopes; Strontium Radioisotopes; Time Factors