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Biomedical subjects

A Luz

Publications and source records attributed to A Luz.

At least 91 records · Page 5Linked to original sources

Oncogenic retrovirus from spontaneous murine osteomas. I. Isolation and biological characterization.

Spontaneous osteomas in strain 101 mice, a strain which has a high incidence of benign bone tumours, harbour numerous C-type virus-like particles with pleomorphic characteristics. A cell-free extract from osteomas from two mice induced bone tumours, together with osteopetrosis and lymphomas, in newborn mice of the low incidence NMRI strain after a latent period of 12 to 15 months. When C3H embryo fibroblasts were infected with the osteoma extract, the resulting cell line produced virus (OA MuLVC) with a high titre. OA MuLVC was cloned by serial endpoint dilution and NIH 3T3 cells were productively infected. The resulting virus was named OA MuLVN. OA MuLVC and OA MuLVN also induced bone tumours, osteopetrosis and lymphomas 12 to 15 months after injection into newborn NMRI mice. The isolated virus showed typical characteristics of the murine retrovirus group. Fv-1 host range restriction assays classified the viruses as N-ecotropic and XC-positive. Tryptic p30 peptide analysis and RNase T1 fingerprint analysis of OA MuLVC and OA MuLVN indicated that OA MuLVC contains an Akv-like virus as well as additional components, whereas OA MuLVN is closely related to Akv, but not identical to it. Serological analysis of the envelope proteins using monoclonal antibodies also showed the virus to be similar, but not identical, to Akv virus.

Animals↗

RNA-tumorviruses, oncogenes, and their possible role in human carcinogenesis.

The detection and characterization of oncogenes via RNA tumor viruses (or retroviruses) and the recognition of their location at breakpoints of chromosomal translocations which are frequently found in certain human neoplasms has promoted present understanding of molecular mechanisms underlying carcinogenesis. Oncogenes are cellular genes which can be transduced by RNA tumorviruses and induce malignant transformation under experimental conditions in vivo and in vitro. A role of retroviruses in human leukemogenesis is suggested by epidemiological observations and by the isolation of such viruses from several human T-cell leukemias and lymphomas (human T-cell leukemia/lymphoma virus or HTLV) as well as by biochemical association of retroviral markers with human leukemias. A role of HTLV has been suggested also in a human immune deficiency syndrome (AIDS). In view of the well known role of many factors in carcinogenesis the concept of carcinogenesis as a multistep process as well as the concept of cocarcinogenesis and the role of cofactors other than viruses, such as radiation and chemicals, aging, hormones, graft vs host reaction, environmental factors etc., will have to be carefully considered.

Acquired Immunodeficiency Syndrome↗

226Ra induced bone-cancers: the effects of a delayed Na-alginate treatment.

At the present time no unequivocal evidence exists which shows that a reduction in the body-burden of a radionuclide by decorporative treatment results in a proportional decrease in the risk of long-term radiation effects. We have investigated the effectiveness of the daily administration of Na-alginate via the diet in removing 226Ra from the skeleton and in reducing the number of late effects such as osteosarcomas. The animals used were male C57Bl mice which had been injected with one of three different amounts of 226Ra (4.4, 10.7 or 24.8 kBq) four days prior to the onset of the decorporative treatment. The results showed that although this treatment was able to produce a substantial reduction in the 226Ra content of the mice it did not reduce the incidence of osteosarcoma. These results question the effectiveness of decorporation procedures initiated at longer times after contamination.

Alginates↗

The role of time-factor and RBE for the induction of osteosarcomas by incorporated short-lived bone-seekers.

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.

Animals↗

Increased urinary levels of RNA catabolites in mice as early indicators for malignant growth.

It is known that human cancer patients exhibit an altered urinary excretion pattern of modified nucleosides and bases, that mice bearing skin tumors excrete increased amounts of various modified nucleosides and bases, and that the onset of altered excretion of modified RNA constituents precedes tumor diagnosis. We have now obtained similar results in mice for lymphoblastic leukemia induced by a single exposure to X-ray irradiation. Mice showing severe leukemic symptoms excrete severalfold amounts of modified nucleosides in their 24-hr urine, when compared with untreated controls. X-ray-treated mice, showing no visible symptoms except increased excretion rates of these RNA constituents, were sacrificed and histologically examined. (Pre)leukemic features in spleen and lymph nodes were observed. Our results provide further evidence in support of the use of RNA catabolites as a basis for the development of an early noninvasive screening method for cancer in human beings.

Animals↗

Time course of C-type retrovirus expression in mice submitted to osteosarcomagenic doses of 224radium.

Virus particles with the biochemical properties of C-type retroviruses appeared transiently in bone tissues of (C3H x 101) f1 hybrid mice early after treatment with 224 Radium; such particles were then again detected in the bones of the irradiated animals at the onset of osteosarcoma formation and in the osteosarcomas. Antibodies against a murine retrovirus isolated from a 224 Ra-induced osteosarcoma were produced and detected in the serum of the 224 Ra-treated animals within a month after treatment began. The antibody levels plateaued to a maximum after about 2 months and remained elevated until the tumors started to develop. The antibody concentration in the serum of these irradiated animals decreased then progressively to reach levels similar to those observed in untreated controls. It thus appears that the imminence of osteosarcoma development can be predicted by monitoring the anti-C-type virus antibody levels in the serum of the irradiated mice. These experiments also strongly suggest that treatment with 224Radium induces expression of endogenous viruses in the animals.

Animals↗

Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas.

Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed.

Animals↗

[So-called fibrous long-spacing collagen in a murine osteosarcoma (author's transl) ].

Peculiar periodically banded structures were found in the extracellular spaces of a vascular type of a murine osteosarcoma. The structures consisted of fine almost parallely arranged filaments with electron-dense cross-bands of about 35-50 nm thickness. The periodicity of the bands was about 85-100 nm. Similar structures have been found by many authors in various tissues of different species. Commonly, they have been referred to as "fibrous long-spacing collagen".

Animals↗