Showing papers on "Friend leukemia published in 1978"

Alteration of cellular ribonucleases associated with murine oncogenic virus infection.

Abstract: The ribonuclease activity of peripheral lymphocytes from Balb/c mice was studied at various intervals subsequent to infection of mice by oncornavirus. Lymphocytes from mice infected with Friend leukemia virus possessed elevation of RNase activity within 8 days subsequent to infection. Balb/c mice infected with Moloney sarcoma virus demonstrated an analogous elevation of RNase activity with 7-9 days postinfection. Diminishment of cellular RNase activity occurred in the Friend leukemia model concomitant to the occurrence of significant numbers of erythroblasts in the peripheral blood, while ribonuclease activity in lymphocytes from mice infected with Molney sarcoma virus returned to normal 1-2 weeks subsequent to host rejection of tumor. It is concluded that elevation of RNase activity within the lymphocyte represents an early event in oncogenic viral infection within these two tumor models. The possible meaning of elevation of RNase activity is a target (the lymphocyte) not predestined to undergo neoplastic transformation is discussed.

Tumor neutralization, immunotherapy, and chemoimmunotherapy of a Friend leukemia with cells secondarily sensitized in vitro: II. Comparison of cells cultured with and without tumor to noncultured immune cells.

Abstract: The aim of this study was to determine if cells primed in vivo could be rendered more effective in killing tumor by secondary sensitization in vitro . C57BL/6 mice were primed with a viable antigenic syngeneic Friend leukemia (FBL-3). The immune spleen cells secondarily sensitized by 5-day culture with irradiated FBL-3 (CiFx) became significantly more effective than fresh noncultured immune cells (Ci) in in vitro cytotoxicity, tumor neutralization (Winn assay), and immunotherapy of an early leukemia. However, in chemoimmunotherapy of advanced leukemia, CiFx were no more effective than Ci. Moreover, Ci cultured with irradiated C57BL/6 spleen cells (CiCx), i.e., without secondary sensitization in vitro , became markedly less effective than noncultured Ci. C57BL/6 mice inoculated with 5 × 10 6 FBL-3 on day 0 received on day 5 cyclophosphamide (CY) plus Ci, CiFx, or CiCx. CY alone doubled the median survival time (MST) to day 26. As an adjunct to CY, Ci or CiFx prolonged the MST to day 53 and day 55 and cured 16/72 and 20/66 mice, respectively, whereas CiCx prolonged the MST to only day 33 and cured 1/36 mice. To determine if the lack of enhanced effect after secondary sensitization in vitro reflects the nature of primary exposure to antigen, other priming regimens were studied. When mice were primed with irradiated FBL-3 or with cross-reacting MSV, CiFx were more effective than Ci in chemoimmunotherapy. Thus, enhancement by secondary in vitro sensitization of primed cells to eradicate advanced leukemia is dependent upon the method of priming and cannot be predicted by results of the in vitro tumor cytotoxicity, tumor neutralization, or immunotherapy of early leukemia. Moreover, primed cells lose effectiveness in tumor therapy if cultured without secondary stimulation.

Mechanisms of genetic resistance to Friend virus leukemia in mice. IV. Identification of a gene (Fv-3) regulating immunosuppression in vitro, and its distinction from Fv-2 and genes regulating marrow allograft reactivity.

Abstract: Friend leukemia viru (FV) suppresses the proliferative response of normal lymphocytes to mitogens. The in vitro suppressive effect of FV on lymphocyte mitogenesis is mediated by T-suppressor cells and is under host genetic control. Lymphocytes from strains of mice of the C57BL background (e.g., C57BL/6) are resistant while cells from other strains (e.g., 129 and DBA/2) are susceptible. Genetic analyses utilizing resistant and susceptible parental strains, their F1, intercross and backcross progeny indicated that susceptibility to in vitro suppression is regulated by a single autosomal gene, dominant for susceptibility to suppression. This gene, which is not linked to the H-2 complex, segregated independently of the Fv-2 gene which controls resistance to spleen focus formation in vivo. The gene is also unlinked to the Ir-like genes which regulate the ability of H-2d mice to reject H-2b bone marrow grafts. The gene is therefore designated as Fv-3. Fv-3 may mediate its effect by regulating the numbers and/or functions of T-suppressor cells.

Origin of spleen colonies generated by Friend virus-infected cells in mice.

Abstract: “Tumor colonies” develop in the spleen of unirradiated C57BL/6 × DBA/2 F 1 (hereafter called BD2F 1 ) mice ( H-2 b /H-2 d ) 9 days after iv injection of spleen cells from N-tropic Friend virus-infected DBA/2 donors ( H-2 d /H-2 d ) To determine whether these spleen colonies resulted from donor or host cell proliferation, we compared the histocompatibility antigen markers of cell populations from dissected colonies and intercolonial areas Cytotoxic tests with mouse antisera specific for H-2D b and H-2D d antigens revealed the presence of both antigen specificities on cells from both sources, thus indicating that the majority of cells were of host BD2F 1 origin The presence of donor cells in spleen colonies could be detected, however, when the recipients were lethally irradiated (800 R) BD2F 1 mice, the colonies of which consisted exclusively of cells bearing H-2D d and not H-2D b (recipient) antigens Analogous results were obtained by cytotoxic analysis of spleen colonies in C57BL/6 × C3H/An F 1 mice injected with Friend virus-infected C3H/An spleen cells In addition, direct visualization of virus-induced antigens and H-2 antigens by immunofluorescent staining confirmed the cytotoxicity data Finally, the colony-forming efficiency of H-2 d cells was found to vary only slightly among unirradiated recipients of different H-2 haplotypes These findings indicate that spleen colony formation by Friend virus-infected leukemia cells was based on donor cell proliferation in irradiated hosts and on host cell proliferation in unirradiated hosts, for the strains used here The spleen colony assay for Friend leukemia cells in unirradiated hosts is therefore an assay for infectious centers where virus is apparently released from donor cells in quantities sufficient to infect Fv-1 -restrictive host cells and to initiate their proliferation

Induction of erythroid differentiation in friend leukemia cells by bromodeoxyuridine

Abstract: Treatment of Friend leukemia cells with BrdU, the thymidine analog which interferes with DMSO induced differentiation in these cells as well as the expression of differentiated character in many other cell systems, is capable of inducing erythroid differentiation. Globin mRNA, as assayed by hybridization to globin cDNA, increases 2.5- to 30-fold after appropriate treatment with BrdU. This effect was observed with several different subclones of three independent Friend tumor cell lines. After BrdU treatment, globin mRNA content may reach up to 10-20% of the levels in DMSO induced cultures. The induction of erythroid differentiation is also apparent when accumulated heme content or the appearance of benzidine positive cells is monitored. One Friend cell line (745) we examined was not induced by BrdU although it incorporated an amount of BrdU into its DNA comparable to that incorporated by the other cell lines. In addition, BrdU did interfere with DMSO induction in this cell line. These results suggest that two different mechanisms may be operative in regulating erythroid differentiation in Friend leukemia cells. While BrdU interferes with the mechanism activated by DMSO treatment, this analog could independently activate an alternative mechanism.

Histidine transfer RNA levels in Friend leukemia cells: stimulation by histidine deprivation.

Abstract: Friend leukemia cells incubated with sublethal concentrations of histidinol for 5 to 6 days show up to twofold increases in their relative concentrations of histidine transfer RNA and no change in the relative concentrations of leucine transfer RNA. A similar effect is seen when cells are grown to stationary phase in the presence of 0.2 times the amount of histidine in Eagle's minimum essential medium. These observations support the theory that the concentrations of specific transfer RNA's are regulated by a mechanism that is sensitive to the extent of their aminoacylation.

Studies on the target cell for the Friend virus (FV-P strain) using the CFU-E technique.

Abstract: In order to characterize the target cell for the polycythemia inducing Friend virus (FV-P) in vivo, mice were treated by induction of plethorism, bleeding, Actinomycin D, and Busulfan before virus infection. The development of the Friend leukemia was then studied mainly using the CFUE technique for erythroid colony growth in vitro. This technique allows the quantification of a new cell type, an erythropoietin (Ep) independent colony forming cell. These Ep independent colonies were taken as marker for the disease. Their number with time after infection was correlated with the compartment size of pluripotent, granuloid committed and erythroid stem cells at the time of infection. The results indicate that the development of the Friend leukemia does not require the actual presence of CFUE, as seen using Actinomycin D, and is not correlated with the number of pluripotent or granuloid stem cells, as seen after Busulfan. It is, however, dependent on the erythropoietic state of the animal, as seen in plethoric mice and mice after bleeding. It is, therefore, concluded that the target cell for FV-P is located within the Ep-responsive cell compartment, between early (BFUE) and late (CFUE) erythroid precursor cells.

H-2 Antigen variants in a cultured heterozygous mouse leukemia cell line : IV. Cell-Mediated cytolysis of wild type and variant cells.

Abstract: H-2 antigen variants, derived from a heterozygous mouse Friend leukemia cell line by selection with anti-H-2 antisera and complement, were tested for susceptibility to cell-mediated cytolysis, using T-lymphocytes directed against individual H-2 antigens. The cytotoxic cells were generated in the BALB and B10 backgrounds by a combination of in vivo and in vitro immunizations. The phenotypes of the variants inferred from the patterns of resistance or susceptibility to CML were consistent with those presumed from earlier assays using antisera. The one exception was the variant cell line which was H-2D(d-) in assays using antisera, but was H-2D(d+) by CML.

Effect of infection of mice with Friend leukemia complex viruses on background antibody-forming cell production in vitro

Abstract: Friend leukemia complex (FLC) and Rowson-Parr virus (RPV) infections of donor mice depress the production of background antibody-forming cells by splenocytes cultured in the absence of specific antigenic stimulation.

H-2 Antigen Variants in a Cultured Heterozygous Mouse Leukemia Cell Line. IV. Cell=Mediated Cytolysis of Wild Type and Variant Cells

Abstract: H-2 antigen variants, derived from a heterozygous mouse Friend leukemia cell line by selection with anti-H-2 antisera and complement, were tested for susceptibility to cell-mediated cytolysis, using T-lymphocytes directed against individual H-2 antigens. The cytotoxic cells were generated in the BALB and B 10 backgrounds by a combination of in vivo and in vitro immunizations. The phenotypes of the variants inferred from the patterns of resistance or susceptibility to CML were consistent with those presumed from earlier assays using antisera. The one exception was the variant cell line which was H-2D d- in assays using antisera, but was H-2D d+ by CML.