Showing papers on "Friend leukemia published in 1987"

Nuclear magnetic resonance analysis of tumor necrosis factor-induced alterations of phospholipid metabolites and pH in Friend leukemia cell tumors and fibrosarcomas in mice.

Abstract: The alterations induced on the pool sizes of five phospholipid metabolites, glycerol 3-phosphorycholine, glycerol 3-phosphorylethanolamine, phosphorylcholine, sn-glycerol 3-phosphate, and choline were studied by nuclear magnetic resonance (NMR) spectroscopy in murine tumors injected with recombinant murine tumor necrosis factor (TNF). Solid tumors were obtained by s.c. injection of either Friend leukemia cells (clones 3C1-8 and 745) in DBA/2 mice or murine fibrosarcoma cells (HeN4) in C3H/HeN mice. After tumor nodules had developed, TNF or bovine serum albumin was injected intratumorally. Treatment of both tumors with TNF resulted in a marked inhibition of tumor growth. 31P-NMR analyses of Friend leukemia cell tumors (and tissue extracts), 6 h after injection of TNF, showed: (a) a 1.5- to 3.5-fold decrease in the pool sizes of glycerol 3-phosphorylcholine and glycerol 3-phosphorylethanolamine; (b) a 7- to 8-fold increase of sn-glycerol 3-phosphate; (c) a 2- to 3.5-fold decrease of phosphorylcholine; (d) an alkaline shift (0.2 units) in intratumoral pH. Similar metabolic alterations occurred in TNF-treated HeN4 fibrosarcoma. 1H-NMR analyses of Friend leukemia cell tumor extracts also indicated, 6 h after tumor injection with TNF: (a) elevated choline levels (9X); (b) a 19-fold increase in the ratio [choline]/[phosporylcholine]; (c) elevated (1.4X) levels of lactic acid; and (d) a 1.6-fold decrease in the [taurine]/[glycine] ratio. The results are interpreted in the light of possible alterations in the activity of enzymes controlling the de novo biosynthesis and catabolism of phospholipids. We concluded that NMR spectroscopy can be a useful means to monitor the level of some phospholipid precursors and/or derivatives as early markers of therapeutic efficacy in intact neoplastic tissues.

Anti-tumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. VI. Adjuvant therapy after surgery in the inhibition of liver and spleen metastases.

Abstract: Adult DBA/2 mice were injected s.c. with the highly malignant, interferon-resistant 3C18 line of Friend erythroleukemia cells (FLC). Eight or 9 days after established s.c. tumors had developed, the primary tumor was excised and mice were treated i.p. with either mouse interferon alpha/beta or a control preparation. At the time of surgery, mice already had tumor cells in the liver. All control-treated mice died in the ensuing 2 weeks with extensive tumor metastases in the liver and spleen. Interferon treatment resulted in an inhibition of the development of liver and spleen metastases and a markedly increased survival time. We conclude that interferon alpha/beta is effective as adjuvant therapy after surgery for metastatic disease in mice.

Cytokinetic effects of bifunctional antitumor intercalator ditercalinium on Friend erythroleukemia cells

Abstract: Ditercalinium (NSC 335153) is a novel 7H-pyridocarbazole dimer in which the two monomers are joined by a rigid bis(ethylpiperidinyl)-linking chain producing a molecule capable of bisintercalation into DNA with extremely high affinity. The effect of ditercalinium on cell proliferation and its interaction with DNA in situ has been investigated in the Friend leukemia cell system. Ditercalinium caused an inhibition of cell growth at 0.5 microM and cell death at 2.5 microM. However, both the cytokinetic and cytotoxic effects became evident only after 1-2 days of continuous drug exposure. In contrast, monointercalators generally affect cell growth within several hours of administration. Furthermore, whereas most intercalators arrest cells in G2 phase, ditercalinium demonstrated no cell cycle phase specificity. In fact, a stathmokinetic experiment, in which vinblastine was used to prevent cell division in exponentially growing Friend leukemia cell cultures, demonstrated that ditercalinium effectively "froze" cells in position throughout the cell cycle, in a dose-dependent fashion. By determining the sensitivity of DNA in situ in fixed Friend leukemia cells to acid-induced denaturation, it was apparent that ditercalinium, rather than stabilizing DNA as do monointercalators, increased the sensitivity of DNA in situ to denaturation induced by acid. It appears, therefore, that the cytokinetic effects and interaction with chromatin of an agent that has the ability to bisintercalate into DNA are qualitatively different from those induced by classical monointercalating drugs.

Erythroid cell fusion in the early phase of Friend virus leukemogenesis

Abstract: Infection of susceptible strain mice with the oncogenic Friend erythroleukemia virus initially results in fulminant erythroid hyperplasia. Several weeks later a frank erythroid leukemia develops. At the earliest stages of Friend disease there is extensive cell fusion involving erythroid cells but not platelets and granulocytes. Fusion was detected in experiments with allophenic (chimeric) mice whose component strains express electrophoretically distinct forms of the dimeric enzyme glucose phosphate isomerase (GPI). Infection of such animals with the polycythemic strain of Friend virus resulted in the rapid development of Friend disease. Concomitant with the appearance of early disease symptoms was the appearance in the red cells of the heterodimeric form of GPI, an unequivocal consequence of cell fusion. Platelet and granulocyte samples from the same infected animals failed to exhibit the hybrid GPI form. Furthermore, no hybrid dimer was evident in red cells from chimeric mice in which blood formation had been stimulated by phenylhydrazine treatment. These observations suggest that the occurrence of cell fusion early after infection by Friend virus is a significant aspect in the rapid development of neoplastic disease.

In vitro and in vivo studies of poly-L-lysine as inducer of friend leukemic cells differentiation

Abstract: Poly-L-lysine, a synthetic cationic polypeptide known for its ability to bind to cell membranes, was found to induce differentiation of Friend leukemia cells "in vitro". Studies were extended to the same "in vitro" model, in order to examine the therapeutic potential of this new differentiating agent. The i.p. administration of the polymer (Mw 2700) at the maximal tolerated dose resulted in major alterations of disease-related parameters. In particular, a multiple treatment schedule on the advanced disease resulted in a successful reduction of target organ weight and peripheral white blood cell count and appreciable differentiation of spleen and bone marrow cells. Apparently, the effects of poly-L-lysine were superior to those produced by N-methyl-acetamide, a potent inducer of differentiation "in vitro".

Interferon and Tumor Necrosis Factor Alter the Phospholipid Metabolism in Friend Leukemia Cell Tumors in Mice

Abstract: Interferon (IFN) has been shown to inhibit the growth of different tumors in experimental animals (reviewed in 1 and 2) and it is currently used to treat some patients with cancer in clinical trials. However the mechanisms of antitumor effects of IFN are still unknown (2). We have previously shown that administration of highly purified α/β IFN was equally effective in inhibiting tumor growth in mice injected with either IFN-sensitive or IFN-resistant Friend leukemia cells (3,4). These data suggested that the antitumor effects of IFN in this system were not due to a direct effect of IFN on tumor cells but that these effects were in some way host-mediated (4). Daily injection of IFN into FLC tumors implanted subcutaneously (s.c.) caused an arrest of tumor growth and tumor necrosis and resulted in a complete tumor regression in some mice transplanted with either IFN-sensitive or IFN-resistant FLC (5).

Reduced maturation of Friend virus in adhesive mutants of Friend leukemia cells.

Abstract: The replication of Friend Leukemia virus (FLV) has been investigated in adhesive clones (FF) of Friend Leukemia cells which were selected via cultivation on top of human fibroblast monolayers. In these adhesive clones a shut-down of FLV production is observed under conditions of culture confluency; this finding is not due either to a reduced number of cell divisions nor to a defective expression of FLV genome as assessed by Northern blot and immunofluorescence studies. Ultrastructural studies showed that virus budding and release into the medium is not detectable under these conditions. Conversely, in confluent FF cell monolayers abundant imperfect type-A enveloped particles were visible, possibly originating from stacks of granular endoplasmic reticulum with thickened membranes.