Showing papers on "Friend leukemia published in 1979"

Effects of 9,10-anthracenedione, 1,4-bis[(2-[(2-hydroxyethyl)amino]-ethyl)amino]-diacetate on cell survival and cell cycle progression in cultured mammalian cells.

Abstract: 9,10-Anthracenedione, 1,4-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-diacetate (NSC 287513), at concentrations ranging from 0.05 to 10.0 µg/ml, altered the cell cycle kinetics of Chinese hamster, Friend leukemia, and SK-L7 cells cultivated in vitro ; the drug had little effect on cycle progression of normal phytohemagglutinin-stimulated lymphocytes. The major effect, following a 2- to 18-hr exposure to drug, was a block of cell cycle progression at the G 2 -M phases as determined by flow cytometry. Although the mode of blocking action was concentration dependent, the results were similar for both a 2- and 18-hr drug treatment. Blocked cells typically had an increased amount of cellular RNA and in some cases abnormally large nucleoli. The terminal point of action in Friend leukemia cells occurred about 3 hr prior to mitosis, or within the last quarter of S phase. Unique to Friend leukemia cells was the observation that after drug treatment, at concentrations of 0.05 to 0.2 µg/ml for 2 to 18 hr followed by cell transfer to normal media, approximately 30% of the cells entered the cycle at a higher ploidy level. Survival curves on treated log phase Chinese hamster cells indicated that the cell kill response was straight line exponential; 50% survival (measured by colony formation) occurred following a 2-hr treatment at 0.7 µg/ml. Stationary-phase-treated Chinese hamster cells were much more resistant to the drug action; 50% survival was observed following a 2-hr treatment at 10 µg/ml. The data suggest that, although the drug-induced cycle block is specific to the G 2 phase, the drug-induced kill is not cycle phase specific.

Unstable resistance of G mouse fibroblasts to ecotropic murine leukemia virus infection.

Abstract: G mouse cells were resistant to N- and NB-tropic Friend leukemia viruses and to B-tropic WN 1802B. Though the cells were resistant to focus formation by the Moloney isolate of murine sarcoma virus, they were relatively sensitive to helper component murine leukemia virus. To amphotropic murine leukemia virus and to focus formation by amphotropic murine sarcoma virus, G mouse cells were fully permissive. When the cell lines were established starting from the individual embryos, most cell lines were not resistant to the murine leukemia viruses. Only one resistant line was established. Cloning of this cell line indicated that the resistant cells constantly segregated sensitive cells during the culture; i.e., the G mouse cell cultures were probably always mixtures of sensitive and resistant cells. Among the sensitive cell clones, some were devoid of Fv-1 restriction. Such dually permissive cells, and also feral mouse-derived SC-1 cells, retained glucose-6-phosphate dehydrogenase-1 and apparently normal number 4 chromosomes. The loss of Fv-1 restriction in these mouse cells was not brought about by any gross structural changes in the vicinity of Fv-1 on number 4 chromosomes.

Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.

Abstract: A latent form of persistent infection can be established in susceptible adult mice inoculated with a preparation of defective Friend spleen focus-forming virus (SFFV) purified free from standard leukemia-inducing helper virus (LLV-F). SFFV persistence was initially observed using an in vivo rescue technique in which SFFV could be directly rescued to form splenic foci of malignant erythropoiesis in mice. At approximately 30 d after virus inoculation however, SFFV could not be rescued after inoculation of LLV-F indicating that persistently infected (i.e., SFFV+) mice were either immume to exogenous helper virus or able to express SFFV-associated defective-interfering (DI) function(s). Persistent infection by SFFV was further documented using an in vitro rescue technique and ultimately resulted in the induction by SFFV of erythroleukemia in the absence of polycythemia or overt virus production. However, SFFV rescued by LLV-F from persistently infected normal and transformed hemopoietic cells was able to induce polycythemia in adult mice suggesting that this is a helper controlled property of the Friend virus complex. Transplantable SFFV-induced erythroleukemic cells could be retrieved from persistently infected yet histologically normal mice. The duration of SFFV persistence in normal spleen tissue suggests that the SFFV provirus resides in either a long-lived or pluripotent hemopoietic cell. Further, certain changes occurred, presumably in the membranes of persistently infected cells, which preceded the overt development of Friend leukemia and facilitated the definition of an SFFV preleukemic phase. Cell surface alterations were revealed using cell transfer techniques. Hemopoietic cells harboring a rescuable SFFV failed to proliferate when inoculated into lethally irradiated, syngeneic adult mice. In contrast, the transformed progeny of preleukemic cell populations and spleen cells transformed by FV complex (i.e., cells replicating both SFFV and LLV-F) were not rejected. This result suggests that histologically normal SFFV+ preleukemic cells express an antigen recognition site which is not present on overtly transformed cells and which may be a pertinent surveillance target for host anti-leukemogenic reactions.

Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.

Abstract: The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.

Dimethyl Sulfoxide-induced Differentiation of Friend Erythroleukemia Cells in the Absence of Cytokinesis

Abstract: Friend erythroleukemia cells grown in culture and induced to differentiate along the erythroid developmental pathway by dimethyl sulfoxide (DMSO) were used as a model system to investigate the requirement for cellular replication to express a differentiated erythroid phenotype. That cytokinesis is not essential for DMSO-induced erythroid differentiation as measured by the synthesis and accumulation of hemoglobin was shown by experiments using cytochalasin B. In these studies, hemoglobin was found to accumulate in Friend cells treated simultaneously with DMSO and cytochalasin B; such treatment caused cells to become enlarged and multinucleated due to inhibition of cytokinesis by cytochalasin B. In contrast, exposure of cells to cytochalasin B for at least 48 hr prior to DMSO caused significant inhibition of erythroid differentiation. The findings support the concept that cellular division and, thereby the production of new cellular types are not required for gene activation and the expression of an erythroid phenotype. These effects of cytochalasin B on DMSO-induced differentiation of Friend leukemia cells also suggest plasma membrane-cytoskeleton involvement in the initiation of the erythroid maturation process in this system.

Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes.

Abstract: Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL.

Effects of a chromatin low molecular weight peptidic fraction on differentiation markers and virus production in Friend leukemia cells.

Abstract: Low molecular weight chromatin peptides exert a dose-dependent inhibition of Dimethylsulfoxide (DMSO)-induced erythroid differentiation of murine Friend Leukemia Cells (FLC). This effect correlates with the degree of purification of the peptide fractions. Crot analysis of globin mRNA amounts in DMSO-treated FLC given the peptides showed a 4-5-fold decrease of messenger RNA in the cytoplasm with no nuclear storage of globin transcripts. Spectrin accumulation in “induced” FLC is inhibited as well. The effects of the peptides on erythroid markers are reversible upon removal of the compounds. They also appear to bespecific forinduced gene expression as (1) no effects are observed on cell growth and RNA synthesis in normalnondifferentiating cell lines; and (2) no changes have been detected with regard to the expression of integrated viral genes coding for continuous shedding of viral particles.

Water permeability changes studied by 17O nuclear magnetic resonance during differentiation of Friend leukemia cells.

Abstract: Water permeability of Friend leukemia cells was studied by 17O nuclear magnetic resonance during differentiation induced by dimethyl sulfoxide (Me2SO). While in noninduced cells water permeability was essentially constant during the growth period, in the Me2SO-induced cells there were two distinct periods at which the water permeability was increased by at least an order of magnitude. These periods correspond to approximately one doubling time and 6 days of growth. This change in water permeability is not due to direct interaction of Me2SO with the membrane but must be ascribed to structural changes in the membrane during the course of differentiation.

Possible Role of the Friend Virus Life Cycle in Differentiating Friend Leukemia Cells Treated with Interferon

Abstract: Friend erythroleukemia cells (FLC) are proerythroblasts chronically infected with the Friend virus complex (FLV, composed by LLV and SFFV). They undergo erythroid differentiation accompanied by synthesis of heme and hemoglobin (Hb), accumulation of globin mRNA and erythrocyte-specific membrane changes upon treatment with DMSO and other polar solvents [6].

Alterations in the Response to Erythropoietin and RNA-dependent DNA Polymerase Activity in Mouse Spleen Cells Infected with Friend Leukemia Virus

Abstract: In order to elucidate the relationship between the development of Friend leukemia and erythroid differentiation in affected organs, C3H/He mice were given injections of high doses (about 2 × 104 spleen focus-forming units) of Friend leukemia virus, and changes in the heme synthesis rate, in responsiveness to erythropoietin in vitro , and in RNA-dependent DNA polymerase activity were investigated. By the 6th day following Friend leukemia virus inoculation, hyperbasophilic “Friend cells” resembling proerythroblasts became dominant in the spleen. The heme synthesis rate in the infected spleen cells started to increase 14 days after inoculation and reached a plateau at a level about five times higher than that of the uninfected control spleen cells after about 22 days. With respect to the response of the spleen cells to erythropoietin in vitro , however, while a normal response had been observed 4 hr after the inoculation, no response could be detected at 24 hr and thereafter. RNA-dependent DNA polymerase activity in the spleen cells began to increase on the 4th day, attaining a peak on the 8th and 10th days and decreasing markedly thereafter. Enzyme activity again increased on the 28th day. These results suggest that Friend leukemia virus affected the erythropoietin-responsive cells at a very early stage of infection, before morphological changes in the spleen cells or increases in RNA-dependent DNA polymerase activity had been observed.

Characterization of Myelomonocytic Leukemia Cells Induced by in vitro Infection of Bone Marrow with FLV

Abstract: The development of systems in which pluripotent haemopoietic stem cells and committed progenitors proliferate and differentiate in vitro has allowed the analysis of factors involved in the regulation of normal haemopoiesis (Bradley and Metcalf, 1966; Pluznik and Sachs, 1966; Axelrad et al., 1974; Stephenson et al., 1971; Dexter and Testa, 1976) and of events associated with leukemia, both in experimental systems (reviewed by Metcalf, 1977) and in patients (e.g. Moore, 1974).

Possible role of DNAse I in the development of experimental leukemia

Abstract: An increase in the DNAase 1 activity in the serum and an increase in the DNAase inhibitor activity in the spleen in the development of virus Friend leukemia were demonstrated. Increased activity of the inhibitor in the spleen was also revealed after intravenous injection of exogenous DNAase 1 into mice. A potential role of serum DNAase 1 in the development of experimental leukemia is discussed.