Friend leukemia

About: Friend leukemia is a research topic. Over the lifetime, 319 publications have been published within this topic receiving 7463 citations.

Effects of ellipticine on cell survival and cell cycle progression in cultured mammalian cells.

Abstract: The effects of ellipticine [5,11-dimethyl-6 H -pyrido(4,3- b )carbazole; NSC 71795] on cell viability, growth, and colony formation were investigated in suspension (Friend leukemia and L1210) and adherent [Chinese hamster ovary (CHO)] tumor cell systems as well as in mitogen-stimulated human peripheral blood lymphocyte cultures. Cell cycle progression and the terminal point of action of the drug were monitored by flow cytometry. Ellipticine was cytostatic for all cell lines tested, blocking cells in G2 phase following 24 hr constant exposure at concentrations in the range of 1.0 µg/ml. A 10 times higher drug concentration was required to block cells in G2 if the cells were exposed for only 30 min to the drug followed by 23.5 hr culture in drug-free medium. Formation of CHO cell colonies was inhibited by 50% following exposure to ellipticine for 2 hr at 6.0 µg/ml or for 24 hr at 0.3 µg/ml. Fifty % cell kill in asynchronously growing Friend leukemia and L1210 cells was obtained following exposure to ellipticine for 24 hr at 2.0 µg/ml and 1.15 µg/ml, respectively, whereas human peripheral blood lymphocytes required 66 hr exposure to 1.0 µg/ml to kill 50% of the cells. Phytohemagglutinin-stimulated lymphocytes were remarkably resistant to the cytotoxic effect of ellipticine but did display a dose-dependent inhibition of stimulation and accumulation in G2 whether the drug was added prior to or during active cell proliferation. Ellipticine, at cytostatic concentrations, had a marked effect on cellular RNA content. Friend leukemia cells, blocked in G2 by the drug, doubled their RNA content compared to control cells. L1210 and CHO cells, but not lymphocytes, also increased in RNA content following ellipticine treatment. Drug concentrations which blocked cells in G2 also led in the case of Friend leukemia and L1210 but not CHO cells to an increase in the proportion of cells with greater than 4C amounts of DNA.

Clonal analysis of early and late stages of erythroleukemia induced by molecular clones of integrated spleen focus-forming virus

Abstract: The integrated proviral DNA of the polycythemia-inducing isolate of Friend spleen focus-forming virus (SFFVp) has been identified in rat cell clones nonproductively infected with this replication-defective erythroleukemia virus and cloned in phage lambda vectors. These lambda SFFVp recombinants, lambda SFFVp502 and lambda SFFVp542, contain endonuclease EcoRI inserts of size 7.4 and 8.2 kilobases, respectively, and include full copies of the SFFVp genome, along with host flanking sequences. Infectivity of the cloned SFFVp genomes was tested by a two-step DNA transfer procedure involving transfection of the cloned DNA into 3T3 mouse fibroblasts or cotransfer of the cloned DNA into thymidine kinase-deficient 3T3 cells together with the cloned thymidine kinase gene of herpes simplex virus, followed by rescue of the transferred DNA by superinfection with a helper virus. Inoculation of the rescued virus into adult mice resulted in the appearance of spleen foci, rapid splenomegaly, and polycythemia. Early after infection, spleen cell populations contained large numbers of cells capable of forming small erythroid colonies in vitro (CFU-E) in the absence of erythropoietin. Late after infection, these mice contained cells capable of forming macroscopic colonies (CFU-FV) in vitro. These data indicate that molecular clones of SFFVp, in conjunction with a helper virus, induce the appearance of hemopoietic colony-forming cells characteristic of both the early and late stages of Friend leukemia.

Influence of synthetic double-stranded ribonucleic acid, poly I:C, on Friend leukemia in mice.

Abstract: SummaryStudies were carried out to measure the effect on Friend leukemia in BALB/c mice of synthetic double-stranded RNA, Poly I:C (rI:rC), given in different prophylactic and therapeutic regimens. The effect of Poly I:C was strongly influenced by the time of initiating treatment, the amount of drug given, and the number and frequency of doses administered. Necrosis and hemorrhage of the spleen were among the principal pathologic effects of Friend leukemia in mice and these were markedly reduced in those instances in which drug treatment decreased splenomegaly. When administered prior to virus, cortisone greatly increased splenomegaly in Friend leukemia both alone and in combination with Poly I:C. The effect of Poly I:C administration before virus was strongly dose-related and a significant beneficial effect was obtained when the amount of drug was reduced to 4 μg. In toto, Poly I:C was not strikingly beneficial in altering the events in experimental Friend leukemia. The complex and multifaceted relations...

Granulocytic stem cells in Friend leukemia.

Abstract: Friend virus induces a leukemia characterized by the proliferation of neoplastic hematopoietic cells believed to be erythroid precursors. In vitro studies were conducted with spleen cells from mice with terminal Friend leukemia in order to determine their capacity for leukocytic differentiation. Spleen cells were obtained from leukemic DBA/2 mice 1 to 2 days before anticipated death and cultured in the presence or absence of colony-stimulating activity (CSA). Growth in liquid culture in diffusion chambers was dependent on CSA and resulted in the generation of normally differentiated granulocytes and macrophages. Colony formation in agar was also dependent on CSA, and the cloning efficiency of leukemic spleen cells was found to be approximately 10 times normal. The colonies formed were composed of leukocytes, which appeared morphologically normal. Total in vitro colony-forming units per leukemic spleen exceeded normal by more than 300-fold, but cells elaborating CSA were decreased. Although it is uncertain whether the stem cells stimulated by CSA are “normal” or “leukemic,” it is clear that Friend leukemia has profound effects on the proliferation and differentiation of nonerythroid stem cells.