strontium-radioisotopes and Lymphoma

Topics: Analgesics, Non-Narcotic; Bone Neoplasms; Humans; Iodine Radioisotopes; Lymphoma; Organometallic Compounds; Organophosphorus Compounds; Palliative Care; Radiotherapy; Radium; Strontium Radioisotopes; Synovial Membrane

We reviewed the outcome of the 10 patients (13 eyes) with localized, biopsy-proven, low-grade lymphoma of the conjunctiva treated at our Department between 1988 and 1997. All patients were treated by beta-ray brachytherapy using a bidirectional 90Sr-90Y ophthalmic applicator (Applicator SIA 2, Amersham plc). Total doses, prescribed at the surface of the applicator, varied between 40 Gy and 80 Gy. With a median follow-up of 78 months (range: 14 to 146 months), seven patients remained with no evidence of relapse (67.5% 10 year disease free survival). Local control was achieved in 10 out of 13 eyes (76.9%). Two of the three local relapses were marginal. One of these three patients also developed a metachronous lymphoma in the contralateral conjunctiva. These three patients underwent a second course of brachytherapy with 90Sr/90Y and remained free of second relapse 109, 68 and 33 months after salvage therapy. No cases of systemic relapse were observed. Late (LENT-SOMA) complications were of grade 2 in five eyes, of grade 3 in one eye and of grade 4 in one eye. Late complications of grade 2 or higher were observed in one out of five patients (20%) treated with doses lower or equal to 50 Gy and in six out of eight patients (75%) treated with doses higher than 50 Gy (P=0.086). Our data indicates that beta-ray brachytherapy was ultimately able to control most conjunctival lymphomas but carried a risk of late complications and marginal relapses that was possibly higher than the rates reported for other radiotherapy techniques.

Topics: Adult; Aged; Brachytherapy; Conjunctival Neoplasms; Disease-Free Survival; Female; Humans; Lymphoma; Male; Middle Aged; Radiation Injuries; Retrospective Studies; Risk Factors; Strontium Radioisotopes; Treatment Outcome; Yttrium 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

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

Treatment of mice with the long-lived bone-seeking radioisotope 89Sr results in the selective irradiation and destruction of the bone marrow. This is accompanied by a marked reduction in natural killer cell activity against YAC-1 lymphoma [NK(YAC-1)]. To test for the presence of cellular suppressors of NK(YAC-1) in 89Sr-treated mice, in vitro and in vivo cell mixture protocols were used. In vitro, we did not observe any specific inhibitory effect of spleen cells from 89Sr-treated mice on NK(YAC-1) activity of normal spleen cells. The NK(YAC-1) activity of 89Sr-treated mice, measured in vivo by their ability to clear radiolabeled YAC-1 cells from the lungs, was impaired. However, spleen cells from 89Sr-treated mice, when adoptively transferred with normal spleen cells, failed to inhibit the NK(YAC-1) activity of the latter in the lung clearance assay. Further, when normal spleen cells were injected into 89Sr-treated mice, the ability of the transferred cells to mediate in vivo activity was not suppressed in the 89Sr-treated host. These experiments support the suggestion that the low NK(YAC-1) activity in 89Sr-treated mice is not mediated by suppressor cells, but may be due to the destruction of the marrow microenvironment which is essential for the generation of functional NK(YAC-1) cells.

Topics: Animals; Cytotoxicity, Immunologic; Immunity, Cellular; Immunization, Passive; Leukemia, Erythroblastic, Acute; Lymphoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Spleen; Strontium Radioisotopes; T-Lymphocytes, Regulatory

(C57BL/6 X DBA/2)F1 hybrid (B6D2F1) mice resist the growth of parental-strain (B6) EL-4 lymphoma cells inoculated intraperitoneally; that is, B6D2F1 mice survive longer than B6 mice and do not develop ascites. As compared with B6 mice, B6D2F1 mice have higher levels of natural killer (NK) activity against 51Cr-labelled EL-4 cells in their lymphoid organs. B6D2F1 mice treated with 89Sr lose NK activity for certain lymphoma cell targets, e.g. YAC-1, but NK(EL-4) function is usually intact. However, 89Sr-treated mice had lost hybrid resistance to EL-4 cells in vivo, as determined by survival by irradiated or unirradiated EL-4 cells, Corynebacterium parvum, or polyinosinic:polycytidylic acid (pI:pC) in spleens of normal B6D2F1 mice, but NK(EL-4) activity was depressed within 3 days by such treatment in B6D2F1 mice previously injected with 89Sr. Suppressor cells for NK(EL-4) but not for NK(YAC-1) effectors were easily detected in spleens of 89Sr-treated mice "challenged' with C. parvum. Thus, agents capable of stimulating NK cell function in normal mice may lead to suppression of that activity in mice depleted of marrow-dependent cell function by 89Sr. Spleen cells of 89Sr-treated B6D2F1 mice were also unable to generate anti-EL-4 cytotoxic T lymphocytes in a cell-mediated lympholysis system; this defect appeared also to be mediated by suppressor cells. Lymphoid cells depleted by 89Sr-induced marrow aplasia may have two functions in host defences against tumours (especially lymphomas): they may lyse tumour cells directly and they may "down-regulate' suppressor cells capable of inhibiting other "natural' or "induced' immune functions.

Topics: Animals; Cell Line; Cytotoxicity, Immunologic; Female; Hybridization, Genetic; Killer Cells, Natural; Lymphoma; Male; Mice; Neoplasms, Experimental; Propionibacterium acnes; Spleen; Strontium Radioisotopes; T-Lymphocytes; T-Lymphocytes, Regulatory

Treatment of BALB/c mice with radioactive isotopes of the bone-seeking element strontium reduces the percentage of specific NK-cell cytotoxicity to only 2.6%, compared with 13.6% for normal BALB/c and 36.3% for athymic (nude) BALB/c. The syngeneic plasmacytoma NS-1 was used as target in a 4th in vitro NK-cell microassay. Marrow cellularity in treated mice is reduced to 12.5% of controls, but haemopoietic and stem-cell functions are taken over by the spleen and the peripheral blood picture remains relatively normal. Allogenic (H-2k) tumour transplants are rejected normally with good anti-H-2k alloantibody response. Haemopoietic and T- and B-cell functions are therefore substantially intact, and the defect seems confined to NK cells. In vivo, after s.c. inoculation of 10(6) NS-1 cells, 8/12 controls grew a solid tumour after a mean delay of 30.5 +/- 1.25 (s.e.) days, whereas 5/6 90Sr-treated mice grew the tumours after a delay of only 10.5 +/- 1.8 days. This markedly reduced delay in the 90Sr-treated mice lends support to suggestions that NK cells play an important role in resisting the establishment of tumour foci (i.e. in antitumour surveillance). Mice treated with 90Sr could be useful in evaluating the in vitro role of NK cells.

Topics: Animals; Cell Line; Cell Survival; Female; Killer Cells, Natural; Lymphoma; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Biological; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Strontium Radioisotopes; Time Factors; Transplantation, Homologous

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

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

Topics: Animals; Binding Sites; Bone Marrow Transplantation; Female; Interferon Inducers; Interferons; Killer Cells, Natural; Lymphoma; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Nude; Spleen; Strontium Radioisotopes; Transplantation, Isogeneic

Single intraperitoneal doses of soluble 90Sr and monomeric 239Pu induced generalized lymphomatosis in laboratory mice. Leukaemogenesis due to soluble 226Ra was more uncertain. Clinical expression was variable, but as a generalization the disease was a lymphosarcoma with haematogenous (leukaemic) spread. Only rarely, unlike the commonly recorded forms of natural and X-ray-induced lymphosarcomas, was the thymus apparently the site of onset. The cell-type was lymphoblastic of undifferentiated null form (not T, not B). The average doses of alpha or beta radiation accumulated in the bone-marrow, the presumed site of induction, were at the time of diagnosis usually more than 2500 rad, but, if the cases occurring after radium or low activities of plutonium are accepted as induced, 300-1500 rad of alpha radiation. Mice converted to chimaeras only rarely exhibited any lymphoma, general or local. Abdominal lymphomas were not numerically increased by these radionucleides (perhaps due to shortening of life-span) though some may have been prematurely induced.

Topics: Animals; Chimera; Female; Leukemia, Experimental; Leukemia, Radiation-Induced; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Neoplasms, Experimental; Plutonium; Radium; Strontium Radioisotopes

NK cells with lytic capacity for Moloney leukemia virus-induced lymphomas have previously been found to occur spontaneously in spleens from nonimmune adult mice. Here, 89Sr-treatment is shown to suppress NK cell function in adult mice without similarly affecting other cell-mediated immune reactions. Thus, selective 89Sr-sensitivity distinguishes NK cells from other killer cell types. The present results indicate that in vivo a functional bone marrow is needed for generation and maintenance of NK activity.

Topics: Animals; Antigens, Neoplasm; B-Lymphocytes; Bone Marrow; Cytotoxicity Tests, Immunologic; Female; Immunity, Cellular; Lymphoma; Male; Mice; Mice, Inbred A; Mice, Inbred C57BL; Mice, Inbred CBA; Moloney murine leukemia virus; Neoplasms, Experimental; Spleen; Strontium Radioisotopes; T-Lymphocytes

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

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

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 Membrane; Cell Nucleus; Cytoplasm; Epithelial Cells; Epithelium; Lymphoma; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Microscopy, Electron; Neoplasms, Experimental; Radiation Dosage; Radiation Effects; Reticulocytes; Strontium Radioisotopes; Thymus Gland; Thymus Neoplasms

Topics: Animals; Bone Marrow; Bone Marrow Cells; Dose-Response Relationship, Radiation; Female; Hematopoiesis; Leukocytes; Lymphoma; Mice; Mice, Inbred CBA; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Radiation Effects; Spinal Cord Neoplasms; Spleen; Strontium Radioisotopes; T-Lymphocytes; Thymus Gland; Thymus Neoplasms

Topics: Animals; Antibody Formation; Basophils; Bone Marrow; Hematopoietic Stem Cells; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma; Primary Myelofibrosis; Radiation Effects; Strontium Radioisotopes; Swine; Swine Diseases