The Regulation of Differentiation in Murine Virus-Induced Erythroleukemic Cells

Cloned interferon-sensitive (745) and interferon-resistant (3Cl-8) Friend erythroleukemia cells (FLC) passaged in vitro, are not very tumorigenic when first injected intraperitoneally (i.p.) into syngeneic DBA/2 mice although they do form solid tumors when injected subcutaneously (s.c.). By serially passaging FLC (either 745 or 3Cl-8 cells) i.p. in DBA/2 mice, we obtained two different FLC lines capable of growing i.p. and inducing tumor ascites. The s.c. injection of DBA/2 mice with these in vivo passaged FLC resulted in tumor metastases in the liver and spleen, whereas metastases were not observed in mice inoculated s.c. with in vitro passaged FLC. The capacity of in vivo passaged FLC to metastasize was acquired after several i.p. passages. This highly malignant behavior was a stable characteristic of these cells. All the clones derived from in vivo passaged FLC and passaged more than 14 times in vitro induced hemorrhagic ascites when injected i.p., and metastasized to the liver and spleen when injected s.c. The phenotype of sensitivity or resistance to the inhibitory effect of alpha/beta mouse interferon on virus replication and cell multiplication was conserved during serial i.p. passages and maintained in the clones derived from in vivo passaged cells. These FLC showed a decreased capacity to differentiate in vitro upon treatment with dimethylsulfoxide (DMSO) and a reduced production of Friend leukemia virus with respect to the original clones passaged in vitro.

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“…

(Friend, 1978). FLC clones maintained in vitro for several years are not very tumorigenic when first injected intraperitoneally (i.p.)

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confidence: 99%

Biologic and biochemical differences between in vitro and in vivo passaged friend erythroleukemia cells. I. Tumorigenicity and capacity to metastasize

Belardelli

Ferrantini

Maury

et al. 1984

Intl Journal of Cancer

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“…Friend virus-transformed murine erythroleukemic cells (FELC) have been extensively studied [12,13]. They grow in culture as undifferentiated proerythroblasts but can be induced to differentiate along the erythroid pathway to orthochromatic normoblasts by various chemicals including dimethylsulfoxide (DMSO) [13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Murine Tumor Necrosis Factor on Friend Erythroleukemic Cells

1985

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Tumor necrosis inducing factor (TNF), a 140,000 molecular weight glycoprotein present in the serum of Corynebacterium parvum endotoxin-treated mice, was cytotoxic toward Friend virus-transformed erythroleukemic cells (FELC). These cells grow in culture as undifferentiated pro-erythroblasts but can be induced to differentiate in a limited fashion along the erythroid pathway to orthochromatic normoblasts by various agents such as dimethylsulfoxide (DMSO). Partially and highly purified preparations of TNF were cytotoxic toward logarithmically growing FELC whereas a comparable serum protein fraction from C. parvum treated mice or endotoxin from E. coli had no effect upon FELC viability. DMSO-induced cells were more sensitive to the action of TNF requiring only about half the concentration needed to produce 50% kill in noninduced cells. Inhibition of hemoglobin formation was TNF dose-related and could be decreased by 94%. TNF was also cytotoxic toward DMSO-induced cells in stationary phase and mitomycin C treated noninduced FELC. Neuraminidase modification of the surface of FELC increased the cytotoxicity of TNF by 50%. These results demonstrate that TNF destroys FELC whether they are nondividing, dividing or partially differentiated and suggest that TNF may accomplish this by affecting cell metabolism after internalization.

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“…DMSO is known to alter cell membrane permeability and trigger differentiation in cer tain cell lines. For example, Friend leukemia cells are nucleated erythroid precursors which, when treated with DMSO, differentiate [8] and also produce a 2-fold greater amount of Friend leukemia virus-specific RNA in the cytoplasm [9,10]. This finding suggests that differentiation produces a cell which is more tolerant of virus production.…”

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confidence: 54%

Transformation in the Presence of Dimethyl Sulfoxide Facilitates Recovery of Epstein-Barr Virus

Wilson¹

1983

Intervirology

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Human umbilical cord blood lymphocytes were immortalized by infection with Epstein-Barr virus (EBV) in the presence of various concentrations of dimethyl sulfoxide (DMSO). 13 continuous lymphoblastoid cell lines were established. DMSO did not affect the efficiency of transformation and establishment of these lines. After a period of 2 months in culture, the lines were tested for EBV production by lethal irradiation (6,000 rad) from a ⁶⁰Co source and subsequent cocultivation with primary umbilical cord lymphocytes. Cell lines transformed in the presence of 2% DMSO yielded transforming activity in 46.6% of test cultures, compared with 9.5% for lines established without DMSO in the medium. These findings imply that a permanent change in the host/virus relationship resulted from a brief exposure (48 h) to DMSO at the time of transformation.

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The Regulation of Differentiation in Murine Virus-Induced Erythroleukemic Cells

Cited by 20 publications

References 62 publications

Biologic and biochemical differences between in vitro and in vivo passaged friend erythroleukemia cells. I. Tumorigenicity and capacity to metastasize

Biologic and biochemical differences between in vitro and in vivo passaged friend erythroleukemia cells. I. Tumorigenicity and capacity to metastasize

Effects of Murine Tumor Necrosis Factor on Friend Erythroleukemic Cells

Transformation in the Presence of Dimethyl Sulfoxide Facilitates Recovery of Epstein-Barr Virus

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