strontium-radioisotopes and Osteosarcoma

Topics: Bone Neoplasms; Child, Preschool; Female; Humans; Osteosarcoma; Pain; Palliative Care; Strontium Radioisotopes

The biological effect of a radiopharmaceutical depends heavily on the heterogeneity of the uptake in the various tissues. A comparative study of two radiopharmaceuticals should therefore include a comparison of the uptake patterns in different tissues. To eliminate the problems caused by variation in kinetics and tumour characteristics between individuals, such a comparison should be based on measured distributions of the radiopharmaceuticals in the same tissue sample. The excellent linearity between activity and counts in images obtained with a digital silicon strip detector allows such distributions to be derived from two autoradiographs acquired at different time points. This method was applied in a comparison of the uptake patterns of 153Sm-EDTMP and 89SrCl2 in sections obtained from a dog with spontaneous osteosarcoma, containing both tumour and normal bone tissues. As the areas of the section were larger than the detector area, the section had to be cut into smaller parts. Images of these were later merged by means of image processing techniques. There were significant differences in the uptake patterns of the two nuclides. In the primary tumour, the uptake of 153Sm was highly heterogeneous, while 89Sr was more uniformly distributed. In trabecular bone, the accumulation of 153Sm was higher than that of 89Sr. In solid cortical bone, 89Sr had the highest uptake.

Topics: Animals; Autoradiography; Bone Neoplasms; Dog Diseases; Dogs; Organometallic Compounds; Organophosphorus Compounds; Osteosarcoma; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Samarium; Strontium; Strontium Radioisotopes

The primary object of this experiment was to evaluate the potential role of the antioxidants, selenium and vitamin E, in the anti-tumour defence of mice internally irradiated with 90Sr. Comparison in terms of neoplastic response was made between mice kept on a selenium and vitamin E deficient diet and mice given the same deficient diet but administered selenium and/or vitamin E in a controlled manner. The influence of simultaneous oestrogen treatment, known to promote radiogenic osteosarcoma induction, was also investigated. Non-irradiated mice were used as controls. Results are presented as crude and actuarial tumour incidence. No significant difference in tumour yield or actuarial tumour incidence was found when the differently treated mouse groups were compared, and accordingly no support was gained for the theory that the antioxidants selenium and vitamin E constitute a critical part of the complex defence system against neoplasms.

Topics: Actuarial Analysis; Animals; Estrogens; Female; Food, Fortified; Incidence; Lymphoma; Mice; Mice, Inbred CBA; Neoplasms, Experimental; Osteosarcoma; Probability; Selenium; Strontium Radioisotopes; Vitamin E

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

Clonal origin of skin and bone tumors produced by repeated beta-irradiation was determined by using mice with cellular mosaicism created by random X-chromosome inactivation, on the basis of phosphoglycerate kinase-1 (PGK). The backs of female C3H/He (Pgk-1a/Pgk-1b) mice were exposed to beta rays from 90Sr-90Y at a dose of 3 Gy per exposure 3 times weekly until tumors appeared. The cumulative tumor incidence reached 100% 500 days after the beginning of irradiation, as determined by the Kaplan-Meier method. All 8 tumors examined were of a single PGK phenotype: 5 squamous cell carcinomas and 2 osteosarcomas of A-type, and 1 squamous cell carcinoma of B-type. The absence of double PGK phenotype (AB-type) tumors indicated the monoclonal origin of the tumors produced by repeated irradiation.

Topics: Animals; Beta Particles; Bone Neoplasms; Carcinoma, Squamous Cell; Dosage Compensation, Genetic; Female; Mice; Mice, Inbred C3H; Mosaicism; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoglycerate Kinase; Skin Neoplasms; Strontium Radioisotopes; Yttrium Radioisotopes

After noting the limits of a purely morphological approach, either the descriptive methods for classifying certain osteosarcomas, or the techniques connected with these limitations such as particularly limited or non significant sampling, the authors consider the possible contribution of new methods such as immunohistochemistry or in vivo radioisotope tests to improve osseous tumor classification. The latter methods may be particularly useful in clarifying a significant number of difficult diagnoses or in providing information on tumor location, to be combined with morphological observations regarding osteosarcomas.

Topics: Diagnosis, Differential; Diagnostic Techniques, Radioisotope; Humans; Osteosarcoma; Radionuclide Imaging; Strontium Radioisotopes

A series of experiments was conducted to examine the effect of glucan on the reticuloendothelial system (RES) and on the development of 90Sr-induced osteosarcomas and malignant lymphomas in CBA/S mice. Glucan demonstrated a strong RES-stimulating effect, as evidenced by a dose-related increase in lysozyme levels in the plasma and an enlargement of the liver and spleen. Weekly injections of glucan between 150 and 250 days after exposure to 90Sr suppressed the actuarial appearance of the fibroblastic type of osteosarcomas and stimulated the emergence of malignant lymphomas. Glucan itself had no tumorigenic effect in mice not exposed to 90Sr.

Topics: Animals; Bone Neoplasms; Drug Administration Schedule; Female; Glucans; Lymphoma; Macrophages; Male; Mice; Mice, Inbred CBA; Mononuclear Phagocyte System; Muramidase; Neoplasms, Radiation-Induced; Organ Size; Osteosarcoma; Spleen; Strontium Radioisotopes

Ionizing irradiation by incorporated strontium-90 exerts two major effects: it induces tumours (mainly osteosarcomas and lymphoreticular tumours) and depresses the immune system. The interrelation between these functions, i.e. the significance of decreased immunological responsiveness in the oncogenic process, remains unclear. The influence of the 90Sr dose and the role of immune modulation on the tumour yield, were investigated in young adult CBA mice. The animals were exposed to different single doses of 90Sr and, in addition, some groups were subjected to long-term unspecific immune suppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. The present paper (part I) reports on the effects of the treatments on bone tumour responses as reflected by incidence, multiplicity, latency time, histologic characteristics and growth behaviour. The histogenesis of osteosarcomas, as evidenced morphologically by preneoplastic and early neoplastic growth, is illustrated and discussed. The results demonstrate a positive dose-response relationship for osteosarcomas, in which the relative incidences of the various osteosarcoma subtypes were differentially affected. Thus, well-differentiated tumours were gradually replaced by less differentiated types as the dose decreased. A correlation was also observed between the incidence of osteosarcomas and that of assumed preneoplastic lesions in the same bones and sites. Immune suppression by ATx and/or ALG did not distinctly alter the neoplastic or preneoplastic responses at any dose-level of 90Sr.

Topics: Animals; Antilymphocyte Serum; Bone Marrow; Bone Neoplasms; Male; Mice; Mice, Inbred CBA; Neoplasms, Radiation-Induced; Osteosarcoma; Precancerous Conditions; Strontium Radioisotopes; Thymectomy

In mice, endogenous retroviruses are known to be activated during the course of radiation osteosarcomagenesis. Using the Southern blotting procedure, we have studied the presence of somatically acquired proviruses in genomic DNA isolated from seven primary 90Sr induced osteosarcomas and one osteosarcoma cell line, 0-127a1, of the CF1 mouse strain. Specific hybridization probes demonstrated the presence of newly integrated ecotropic proviruses in four primary tumors. Probably, clonally integrated proviruses were present at distinct locations in different subpopulations of tumor cells, reflecting tumor heterogeneity. Genomic DNA isolated from cultured osteosarcoma cells contained different additional MCF-related proviruses. No proviruses were found integrated in the vicinity of c-myc, but a large domain containing the complete c-myc gene was found amplified in one primary tumor (greater than 22 kbp) and in 0-127a1 cells (greater than 39 kbp). Our data suggest that activated retroviruses are not essential for the development of radiogenic osteosarcomas in CF1 mice, but they might be responsible for the deregulated expression of a growth promoting gene in some bone tumor cells.

Topics: Animals; Cell Transformation, Viral; DNA Restriction Enzymes; DNA, Neoplasm; Gene Amplification; Gene Expression Regulation; Mice; Neoplasms, Radiation-Induced; Osteosarcoma; Proto-Oncogene Proteins; Strontium Radioisotopes

Eight hundred and twenty male CBA-mice, 75 +/- 3 days of age were divided into four main series. Three of these; A, B and C were further divided into three subgroups. To these 90Sr was given at three different dose levels alone (A) or in combination with either oestrogen (B) or prednisolone (C). In one series (D) all animals were given only oestrogen. The development of intramedullary oestrogen induced bone formation and the early events of bone tumour induction are reported. The 90Sr activities were selected in such a way that the lowest one would be below, the intermediate beyond and the highest well above the limit of bone tumour induction. Comparing the 90Sr injected animals with those given also oestrogen revealed that oestrogen had no promoting effect at the lowest and intermediate dose levels but increased the tumour incidence with a factor 4 at the highest dose level whereas prednisolone had an inhibitory effect. From the results obtained it was proposed that oestrogen may act only as a preparatory promoter and not assist in the initiating events. As has been reported elsewhere, the frequency of osteoblastic and osteoclastic osteosarcomas was higher in animals given oestrogen and 90Sr than 90Sr only. Mice given only oestrogen did not develop bone tumours.

Topics: Animals; Bone Neoplasms; Cell Division; Estrogens; Male; Mice; Mice, Inbred CBA; Neoplasms, Radiation-Induced; Osteogenesis; Osteosarcoma; Prednisolone; Strontium Radioisotopes

We report a study of strontium kinetics in two patients who received 89Sr therapy for disseminated osteogenic sarcoma, together with estimates of absorbed dose to the principal metastases and to bone marrow. In neither patient did tumour uptake of strontium have a significant effect on whole-body retention. In one patient, whole-body strontium kinetics agreed closely with the ICRP standard model, while in the second, retention was extremely prolonged, probably due to hypertrophic osteoarthropathy. Strontium-85 scintigraphy, surface counting and high-resolution whole-body profiles agreed in showing that in both patients tumour turnover of strontium was very rapid, with a biological half-life of only a few days. Absorbed dose to tumour was found to be comparable in magnitude to the mean bone-marrow dose. We have no reason to believe that 89Sr therapy was of clinical benefit to either patient.

Topics: Adolescent; Adult; Bone Marrow; Bone Neoplasms; Humans; Kinetics; Neoplasm Metastasis; Osteosarcoma; Radiation Dosage; Soft Tissue Neoplasms; Strontium Radioisotopes

Internal irradiation of mice using bone seeking radionuclides results in the activation of endogenous retroviruses and in the subsequent development of bone tumors. Genomic DNA from an osteosarcoma cell line, derived from an 90Sr-induced bone tumor, was cotransfected with the plasmid pSV2-neo into NIH/3T3 cells and G418-resistant transfectants gave rise to colonies in soft agar. Southern blot analysis of these first cycle transformants revealed the presence of extra copies of c-ras. We have analysed the arrangement of ecotropic murine leukemia proviral sequences in seven 90Sr-induced bone tumors and one osteosarcoma cell line of CF1-mice. Integration of ecotropic and/or ecotropic recombinant proviruses seems to be involved in rearrangements of 3' provirus cellular junction fragments occurring in all tumor DNAs analysed, but no indication for site-specific integration was found. We also determined the primary structure of FBR-MuSV, a transforming retrovirus able to induce bone tumors in newborn mice. FBR-MuSV contains sequences from all four exons of the murine c-fos gene, but lacks sequences encoding the first 24 and the last 98 amino acids of the c-fos gene product. The coding region of FBR-MuSV has also undergone two small in frame deletions. Thus, the v-fosFBR-MuSV retains 236 amino acids of the 380 amino acids of the murine c-fos product. In FBR-MuSV-transformed cells two fos-containing mRNAs have been detected: a 3.3-kb full-size genomic RNA and a 2.2-kb subgenomic mRNA as revealed by both fos- and MuLV-hybridization probes.

Topics: Animals; Cell Line; Chromosome Mapping; DNA Restriction Enzymes; DNA, Neoplasm; Gene Expression Regulation; Mice; Neoplasms, Radiation-Induced; Oncogenes; Osteosarcoma; Sarcoma Viruses, Murine; Strontium Radioisotopes

The frequency of 90Sr-induced osteosarcoma development was determined in the mongrel rats subjected to BCG vaccination. Injection of BCG (5 mg per animal) is shown to change the frequency of tumour development and their multiplicity only in male rats which were vaccinated 20 days before nuclide administration. An increase up to 10 mg per animal of BCG dose injected 10 days before 90Sr administration caused the carcinogenesis inhibition irrespective of the sex of the animals.

Topics: Animals; BCG Vaccine; Dose-Response Relationship, Immunologic; Drug Evaluation, Preclinical; Female; Male; Neoplasms, Multiple Primary; Neoplasms, Radiation-Induced; Osteosarcoma; Rats; Sex Characteristics; Strontium Radioisotopes; Time Factors

The histologic type of a classical osteosarcoma may be difficult to determine because of insufficient biopsy material and polymorphism of the tumour. Since osteoformation is directly related to the differentiation and functional capacity of the tumour cells, 85-Sr scintimetry was used to evaluate osteoid formation in 90 patients with classical osteosarcoma. Measurements over an 8-day period from isotope injection revealed a separation of the lesions into three groups, with high, medium and low activity. Compared to histologic classification into osteoblastic, chondroblastic/fibroblastic, the 41 tumours classified as osteoblastic had a high 85-Sr uptake. The anaplastic lesions belonged to the group with low 85-Sr uptake. Scintimetric determination of the functional differentiation of tumoral cells may possibly be of prognostic value in osteosarcoma.

Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Osteosarcoma; Radiography; Scintillation Counting; Strontium Radioisotopes

Experimental chemotherapy using high-dose methotrexate (MTX) with citrovorum factor (CF) was performed on ddN strain mice bearing 89Sr-induced osteosarcoma and the antitumor efficacy was analyzed through autoradiography ([3H]thymidine). The administration was done using sustained infusion via the tail vein using our own device to maintain certain elevated blood levels of the drugs. As the first experiment, MTX was administered to 4 different groups of mice with dose levels of 250, 500, 1,000, 2,000 mg/kg for 6 hours followed by CF 200 mg/kg for 24 hours. It was found that the blood levels of MTX were maintained at 10(-4) M by the dosage of 500 mg/kg, but no higher levels were achieved by increasing dosage. Tissue such as the small intestine and the bone marrow recovered from the toxicity of MTX in about 1 week after the dosage of 500 mg/kg. In tumors, on the other hand, the tissue showed a gradual recovery with time, but the uptake of [3H]thymidine by the tissue was not restored to the pretreatment level. When the antitumor efficacy of a single dosage of 1,000 mg/kg and 2 dosages of 500 mg/kg each with 1 week interval were compared, the latter was definitely more effective. It was, therefore, concluded that the administration of the drugs should be done repeatedly with optimum doses of MTX and CF rather than with ultrahigh doses of MTX and CF all at once.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Methotrexate; Mice; Mice, Inbred Strains; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

The induction of skeletal tumours, which can be classified as osteosarcomas of many different types, is considered to be the primary carcinogenic effect of radiostrontium. In the present report the cell surface morphology in vivo of 90Sr-induced osteosarcoma cells was investigated, since a variety of tumour cells--and especially those investigated in vitro--have been shown to possess morphologic changes compared with their normal counterparts. Using scanning electron microscopy, variations in cell surface morphology were observed in 2 tumour series, which were serially transplanted in mice for 45 and 60 transfer generations, respectively. The slow-growing osteosarcoma cells of the early transfer generations, of osteoblastic as well as fibroblastic type, seemed to have more cytopodia than the fast-growing osteosarcoma cells from later generations. This may be due to the fact that slowly growing cell populations have a large proportion of cells in G1, in which stage there is a higher frequency of cellular cytopodia.

Topics: Animals; Bone Neoplasms; Cell Membrane; Female; Male; Mice; Mice, Inbred CBA; Microscopy, Electron, Scanning; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

In a large series of experiments, fractionated injections of short-lived bone-seekers have been shown in many cases to cause a remarkable increase of the osteosarcoma incidence compared with a single administration of the same total skeletal dose. This effect has been observed with both alpha- and beta-emitters. In addition the latency period was shortened by protracting the dose. The total skeletal doses investigated ranged between 0.9 and 20 Gy for alpha-emitters (224Ra and 227Th) and between 28 and 112 Gy for the beta-emitter (177Lu). In all cases the protracted dose had higher or at least equal effects when compared with a single application. Reference experiments with long-lived alpha- and beta-emitting bone-seeking nuclides (226Ra and 90Sr) showed that the incidence of osteosarcomas per Gy was sometimes lower than that observed when the same skeletal dose was applied by protraction of short-lived radionuclides. The dependence of osteosarcoma incidence on dose-time distribution, duration of internal irradiation, and radiation quality is discussed. In this context the possibility that the critical initial dose rate may be related to the initiating event within the multi-stage hypothesis of carcinogenesis is considered.

Topics: Animals; Bone Neoplasms; Lutetium; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radioisotopes; Radium; Relative Biological Effectiveness; Strontium Radioisotopes; Thorium; Time Factors

Because of the polymorphism of osteogenic sarcomas, examination of a biopsy specimen, which is necessarily small, cannot give an accurate evaluation of the differentiation of the whole tumor. Therefore, a test which provides an overall assessment of the functional capacity of the tumor is needed. For the last ten years, we have been using 85 strontium, which has a metabolism similar to that of calcium and radioactive characteristics that allow external measurements. With this isotope, classification of osteogenic sarcomas is more accurate, ensuring better therapeutic trials.

Topics: Adult; Bone Neoplasms; Child; Humans; Kinetics; Osteosarcoma; Prognosis; Radionuclide Imaging; Strontium Radioisotopes

We treated mice with 89Sr induced osteosarcoma with HD MTX (high-dose methotrexate) and CF (rescue by citrovorum factor), and observed the results of MTX administration. MTX and CF constantly injected through their tail veins at intervals of 6, 24 hours, respectively. The amont of MTX administered ranged from 60 mg/kg to 2,000 mg/kg, while CF administered totalled 200 mg/kg. To determine their antitumor efficacy, we adopted 3H-thymidine based labelling index and mitotic index as well as microautoradiography, and observed how the tumor proliferation had been prohibited. The anti-tumor efficacy was significant when 500 mg/kg of MTX was administered; there was no significant increase in anti-tumor efficacy even after 1,000, 2,000 mg/kg of MTX had been administered. Rather, the tumor was tending to be healed as time passed by after the administration of MTX being 500 mg/kg. Then we administered 500 mg/kg of MTX and 200 mg/kg of CF twice at intervals of 6 days. After we had administered MTX in combination with CF, we started observing the changing condition of the tumor. As a result, we recognized their significant anti-tumor efficacy. The tumor did not show any indication of serious growth. In view of the above, we concluded that it would be more effective to administer repeatedly an optimum dose of MTX and CF than to administer an ultra-high dose of MTX and CF.

Topics: Animals; Drug Therapy, Combination; Leucovorin; Male; Methotrexate; Mice; Mice, Inbred Strains; Osteosarcoma; Sarcoma, Experimental; Strontium Radioisotopes

C57BL/6J mice were used both for induction of osteogenic sarcomas by injection of 90Sr and for induction of sarcomas and carcinomas by injection of 9,10-dimethyl-1,2-benzanthracene. The osteogenic sarcomas had a relatively long induction period; they possessed low immunogenicity and failed to activate splenic suppressor cells either in the original tumor-bearing host or in mice bearing transplanted osteogenic sarcomas. In contrast, and in agreement with previous work, 9,10-dimethyl-1,2-benzanthracene-induced tumors had a relatively short induction period; they possessed high immunogenicity and activated splenic suppressor cells in mice bearing transplanted tumors. These results suggest the possibility that the immunogenicity of tumors correlates with the ability of tumors to activate suppressor cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Neoplasm; Graft Rejection; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Osteosarcoma; Sarcoma, Experimental; Spleen; Strontium Radioisotopes; T-Lymphocytes, Regulatory

From 90Sr-induced primary tumours, three transfer series were established by serial in vivo transplantation. Chromosome counts were obtained from 2 of the primary tumours and 284 transplanted tumours. The recording of abnormalities was limited to numerical chromosome deviations and the occurrence of metacentric configurations. By means of the serial tumour transplantation the numerical chromosome progression was also analysed. Though appearing at different stages of the tumour evolution, similarities in chromosome pattern were observed.

Topics: Animals; Bone Neoplasms; Chromosome Aberrations; Female; Metaphase; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

Mice irradiated with 90Sr in doses of 14.8 and 25.9 kB/q/g body weight were given bone marrow or thymic cells intravenously at monthly intervals, or in single doses at 120 or 170 days after injection of 90Sr. At the low dose level a high incidence of lymphoreticular tumours in all cell treated groups occurred as compared with animals irradiated with 90Sr only. At the high dose level only the bone marrow transplanted group contracted a high incidence of lymphoreticular neoplasia. Furthermore, a somewhat decreased osteosarcoma incidence in the cell transplanted animals appeared to be indicated. However, the results obtained are inconsistent and difficult to evaluate. Therefore, it seems necessary to repeat the experiments, if more precise conclusions should be possible to draw.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Female; Lymphoma; Male; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radiation Dosage; Strontium Radioisotopes; Thymus Gland; Time Factors; Transplantation, Isogeneic

Highly inbred CBA mice were used. The registration of chromosome abnormalities was limited to numerical deviations and the occurrence of metacentric chromosomes. By separate serial transplantation from a 90Sr-induced osteosarcoma two parallel transfer series (B and b) were established. From these series transplantation was also performed to hyperimmunized hosts B (Hi) and b (Hi). Besides differences in mean outgrowth period between B-and b-generations, a variation in chromosome pattern was observed. However, this variation should not be evaluated as a typical chromosomal progression of fast and slow growing tumour series.

Topics: Aneuploidy; Animals; Immunization; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes

This investigation started from serially in vivo transplanted tumours. The chromosome patterns of in vitro cultures and of parallelly and serially transplanted tumours were examined. Cultured cells were also used for retransplantation to mice. When comparing the chromosome counts of the cultured cells and the in vivo transplanted tumours, significant differences were revealed. When retransplanting cultured cells, it was also noticed that a similar chromosome distribution appeared, as previously found in 90Sr-induced transplanted series.

Topics: Animals; Cells, Cultured; Chromosome Aberrations; Chromosomes; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes; Transplantation, Homologous

90Sr was given at three different dose levels (29.6, 14.8 and 7.4 kBq/g b.w.) to groups of mice aged 300, 150, 75 and 25 days. It was found that the incidence of osteosarcomas was highest in the 75-day-old-group and lowest in the two oldest age groups. The frequency of lymphoreticular tumours was inversely dose-related (highest incidence in the lower dose series) and not dependent on age at the time of 90Sr injection. The frequencies of soft tissue tumours indicate that these tumours are more related to age than to the dose employed.

Topics: Age Factors; Animals; Dose-Response Relationship, Radiation; Lymphoma; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Radiation Dosage; Soft Tissue Neoplasms; Strontium Radioisotopes

Transplanted tumours from a 90Sr-induced primary tumour were used as an experimental model to eliminate any connection between the chromosome distribution and outgrowth period of radiation-induced transplanted tumours. For this reason repeated transplantations were performed from different tumours of predetermined age from a transfer generation, to receive separate but parallel transfer generations. From each one of these generations a tumour of the same age as used to establish a particular generation was used for continued transplantation. It was then observed that the percentage of 40-chromosome cells in general decreased with the age of the tumour used for transplantation. Furthermore, early established transfer generations were often characterized by more slow growing tumours. However, it should be realized that even if a true relationship between chromosome pattern and outgrowth period cannot be eliminated, the differences found may be due to accidental variations.

Topics: Age Factors; Animals; Chromosome Aberrations; Male; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Osteosarcoma; Sarcoma, Experimental; Strontium Radioisotopes; Transplantation, Homologous

In chronic strontium-90 administration into rats aged 8--10 months osteosarcomas did not develop, while in animals at the age of 3--4 months osteosarcomas incidence was 6.7%. In single injection of the radionuclide in 8--10 months old animals osteosarcomas developed in 2.2% of observations, whereas in 3--4 months old animals--in 45.7%. The most early appearance of osteosarcomas (at the 193d--316th day) was noted in 3--4 months old animals subjected to a single exposure to strontium-90.

Topics: Administration, Oral; Age Factors; Animals; Neoplasm Metastasis; Neoplasms, Experimental; Osteosarcoma; Rats; Strontium Radioisotopes; Time Factors

Topics: Age Factors; Animals; Bone Neoplasms; Diet; Dogs; Dose-Response Relationship, Radiation; Female; Injections, Intravenous; Male; Myeloproliferative Disorders; Neoplasms, Radiation-Induced; Osteosarcoma; Radium; Respiration; Strontium Radioisotopes; Yttrium Radioisotopes

Topics: Antigens; BCG Vaccine; Bone Neoplasms; Neoplasms, Experimental; Osteosarcoma; Strontium Radioisotopes

Antibodies against non-histone chromosomal proteins for 89Sr-induced osteogenic sarcoma (mouse) were prepared by immunization of rabbits. The immunoreactivity of this antigen was then compared with those of non-histone chromosomal proteins from Ehrlich ascites tumor, normal mouse liver, and calf thymus by the method of quantitative microcomplement fixation. The non-histone chromosomal proteins of 98Sr-induced osteogenic sarcoma, fractionated by hydroxylapatite chromatography, exhibited significant affinity for the antibodies. Similar proteins from Ehrlich ascites tumor, normal mouse liver, or calf thymus were virtually inactive, indicating the tissue-specificity of 89Sr-induced osteogenic sarcoma proteins.

Topics: Animals; Chromosomal Proteins, Non-Histone; Complement Fixation Tests; Epitopes; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Rabbits; Strontium Radioisotopes

A comparative analysis of the data of roentgenography-angiography, scanning and radiometry with strontium-85 in 54 patients showing osteogenic sarcoma and osteoblastoclastoma has demonstrated a relationship between the quantitative characteristics of the radioactive Sr inclusion and the intensity of reactive osteoformation, mineralization of neoplastic tissues, an activity of the pathological process, and the rate of vascularization, as well.

Topics: Adolescent; Adult; Age Factors; Female; Giant Cell Tumors; Humans; Male; Middle Aged; Osteoma, Osteoid; Osteosarcoma; Radiation Dosage; Radiography; Radionuclide Imaging; Strontium Radioisotopes

The development of radiostrontium-induced osteosarcoma was studied in BCG-treated and in untreated control mice. Within the observation period of 420 days after the administration of radiostrontium there was a total tumour-incidence of 89.5 and 90.5 per cent for the respective groups of animals. There was no statistically significant difference between the two groups, neither with regard to the time of the first roentgenographic appearance of the osteosarcoma, nor concerning the total tumour incidence , nor with regard to the distribution of the primary sites of the tumours. The tumours of the BCG-treated animals showed a clear tendency to a slower growth rate in comparison to that of the tumours in the control animals. This effect was probably immunological in nature. The mortality in osteosarcoma following radiostrontium administration, however, showed no significant difference between the two groups. Light microscopical and ultrastructural examination did not disclose any clear structural difference between the tumours from BCG-treated and untreated control animals.

Topics: Animals; BCG Vaccine; Female; Histocytochemistry; Male; Mice; Neoplasms, Radiation-Induced; Osteosarcoma; Sarcoma, Experimental; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Iodine Radioisotopes; Male; Neoplasms, Radiation-Induced; Osteosarcoma; Parathyroid Glands; Rats; Strontium Radioisotopes; Thyroid Gland; Thyroidectomy

Topics: Adolescent; Adult; Aged; Angiography; Bone Neoplasms; Chondrosarcoma; Chordoma; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Osteomyelitis; Osteosarcoma; Sarcoma, Ewing; Strontium Radioisotopes

No statistically significant difference in alkaline phosphatase levels was demonstrated in animals injected with the FBJ virus. However, there was a significant increase associated with the development of osteosarcomas in response to the iv injection of 1.0 uCi 90 Sr/g body weight into 11-18-mo-old Anl:CFl females. It was proposed that alkaline phosphatase determinations can be used as well as roentenographic analysis to detect 90Sr-induced tumors in mice.

Topics: Alkaline Phosphatase; Animals; Bone Neoplasms; Female; Gammaretrovirus; Mice; Neoplasms, Radiation-Induced; Osteosarcoma; Radiography; Rodent Diseases; Sarcoma, Experimental; Strontium Radioisotopes

The rate of tumor incidence in different rhythms of rat stomach exposure to cesium-137 and strontium-90 was analysed. The correlative values of the administered nucleids activity were selected by analogy with their content in global natural fall-out. In single exposure to the concentrations of 400 and 100 mc/per rat of cesium-137 and strontium-90 mixture accordingly, osteogenic osteosarcomas developed approximatley 4 times as frequently as in chronic administration of the same radionucleids in concentrations of 2 and 8 mc/per rat, correspondingly.

Topics: Adenoma; Adrenal Gland Neoplasms; Animals; Cesium Radioisotopes; Female; Lymphoma, Large B-Cell, Diffuse; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Parotid Neoplasms; Rats; Strontium Radioisotopes

Data now available on the risks of radiation-induced fatal cancer and hereditary disease and radionuclide metabolism suggest that limits on the rates of intake of 90Sr, 226Ra and 239Pu at work, presently recommended by the International Commission on Radiological Protection, might be in need of considerable revision one with another and with the limit for uniform exposure of the whole body.

Topics: Body Burden; Breast Neoplasms; Carcinoma; Dose-Response Relationship, Radiation; Female; Genetic Diseases, Inborn; Humans; Leukemia; Lung Neoplasms; Male; Maximum Allowable Concentration; Neoplasms, Radiation-Induced; Nuclear Warfare; Occupational Medicine; Osteosarcoma; Paranasal Sinus Neoplasms; Plutonium; Radiation Injuries; Radiation Tolerance; Radium; Strontium Radioisotopes; Thyroid Neoplasms

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

Groups of female CBA-mice were given 90Sr (14.8 kBq/g-0.4muCi/g--bodyweight) alone or in combination with polyestrodiolphosphate, methylprednisolone or nortestosterone, respectively. When 90Sr was given in the first combination, the frequency of osteosarcomas was significantly increased whereas the tumour latency time was decreased compared to mice given 90Sr alone. In combination with nortestosterone such effects were not found, whereas the combination 90Sr + methylprednisolone resulted in a strong reduction of the osteosarcoma incidence and a prolonged tumour latency time. The latter experiment was repeated in a larger experiment whereby the results were confirmed.

Topics: Animals; Bone Neoplasms; Cocarcinogenesis; Estradiol; Female; Methylprednisolone; Mice; Mice, Inbred CBA; Nandrolone; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Strontium Radioisotopes; Time Factors

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

Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton.

Topics: Adult; Bone Diseases; Bone Neoplasms; Child; Diagnosis, Differential; Evaluation Studies as Topic; Femoral Fractures; Fluorine; Humans; Lymphoma; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteosarcoma; Pelvic Bones; Phosphates; Radiography; Radioisotopes; Radionuclide Imaging; Skull Neoplasms; Strontium Isotopes; Strontium Radioisotopes; Technetium

Comparative studies between radiological (equals R; x-ray, thermography, angiography) and nuclear medical examinations (equals NM; scanner-, scintillation camera-sequential scintigraphy) in 339 patients with different bone diseases led to the following results: Thermography proved to be inferior to scanning in detecting of bone diseases. Angiography was the procedure of choice in detecting malignant bone tumors. Sequential scintigraphy performed by means of the Anger-HP-scintillation camera and Intertechnique-Cine-System allowed to establish the kinetic behaviour of tumors: an early increased TcPoP accumulation was observed in tumors with high perfusion (sarcoma), a late accumulation in those with low perfusion (osteoid osteoma).

Topics: Angiography; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diagnostic Errors; Femoral Neoplasms; Humans; Kinetics; Neoplasm Metastasis; Osteoma, Osteoid; Osteosarcoma; Phosphates; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Thermography; Tibia

Topics: Bone Neoplasms; Humans; Osteosarcoma; Radionuclide Imaging; Strontium Radioisotopes

Tumours induced in mice, either CBA normal and chimaerical, or C3H, by (90)Sr or (226)Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8·6 and 5·2, (2) 1: 9 dimethyl methylene blue (Taylor).It is concluded:(a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts.(b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases.(c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by (90)Sr-(90)Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone).(d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata.(e) Lymphomata also occur when the marrow is irradiated ((90)Sr-(90)Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Clinical Enzyme Tests; Color; Coloring Agents; Fibrosarcoma; Hemorrhage; Histocytochemistry; Lymphoma; Mesenchymoma; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoric Monoester Hydrolases; Plutonium; Radiation Dosage; Radioisotopes; Radium; Staining and Labeling; Strontium Radioisotopes; Succinate Dehydrogenase; Yttrium Isotopes

Topics: Animals; Cell Nucleus; Chromatin; Cytoplasm; Endoplasmic Reticulum; Femur; Inclusion Bodies, Viral; Injections, Intraperitoneal; Lysosomes; Male; Mice; Mice, Inbred CBA; Microscopy, Electron; Mitochondria; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Organoids; Osteosarcoma; Staining and Labeling; Strontium Radioisotopes; Time Factors

Topics: Bone Neoplasms; Chondrosarcoma; Fibrosarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Osteosarcoma; Radiography; Radionuclide Imaging; Sarcoma; Sarcoma, Ewing; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Adolescent; Adult; Child; Diagnosis, Differential; Fibroma; Giant Cell Tumors; Humans; Male; Maxillary Neoplasms; Ossification, Heterotopic; Osteoma, Osteoid; Osteosarcoma; Pain; Radionuclide Imaging; Strontium Radioisotopes

Topics: Animals; Bone Development; Bone Neoplasms; Cell Division; Delayed-Action Preparations; Estradiol; Female; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Organophosphorus Compounds; Osteoblasts; Osteoclasts; Osteosarcoma; Polymers; Radiation Effects; Rats; Strontium Radioisotopes; Time Factors

Topics: Adenofibroma; Adenoma; Adrenal Gland Neoplasms; Animals; Cesium Isotopes; Female; Fibroma; Iodine Radioisotopes; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Parathyroid Neoplasms; Radioisotopes; Rats; Strontium Radioisotopes; Thyroid Neoplasms

Topics: Bone and Bones; Calcium; Calcium, Dietary; Cesium Isotopes; Minerals; Neoplasms, Radiation-Induced; Osteosarcoma; Potassium; Radiation Injuries; Radioactive Fallout; Sarcoma; Soil; Strontium; Strontium Isotopes; Strontium Radioisotopes

Topics: Autoradiography; Bone Neoplasms; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Incidence; Mice; Mice, Inbred CBA; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone and Bones; Bone Neoplasms; Citrates; Citric Acid; Mice; Neoplasms; Osteosarcoma; Strontium; Strontium Radioisotopes; Zirconium

Topics: Animals; Bone and Bones; Bone Neoplasms; Neoplasms; Osteosarcoma; Rats; Sarcoma, Experimental; Strontium; Strontium Radioisotopes

Topics: Bone Neoplasms; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Morphogenesis; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Bone Neoplasms; Dogs; Neoplasms, Experimental; Osteosarcoma; Strontium; Strontium Radioisotopes

Topics: Animals; Arvicolinae; Bone Neoplasms; Fibula; Humans; Neoplasms; Osteosarcoma; Sarcoma; Strontium; Strontium Radioisotopes; Tibia