Showing papers on "Friend leukemia published in 1984"

Inhibition of Dimethyl Sulfoxide-induced Differentiation of Friend Erythroleukemic Cells by 5′-Methylthioadenosine

Abstract: 5′-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro , including the Friend leukemia cell system. We have investigated the role of 5′-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 µm, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 µm (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human β-globin probe. Similar results have been obtained by using 5′- S -isobutylthioadenosine, which is a synthetic structural analogue of 5′-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5′-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5′-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5′-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5′-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation.

Role of interferon and 2'-5'-olygoadenylate synthetase in erythroid differentiation of Friend leukemia cells

Abstract: I t has been suggested that the interferon (1FN)-induced 2’,5’-oligoadenylate (2-5A) synthetase, which polymerizes ATP into a series of 2‘,5‘-linked oligomers with the general formula pppA(2’pB’A),, plays a general role in cell growth and terminal differentiation. For instance, an increase in 2-5A synthetase activity has been described during dimethyl sulfoxide (MezS0)induced erythroid differentiation of Friend leukemia cells (FLC). 2-5A synthetase has been measured in two Friend leukemia cell sublines by various techniques including a radioimmunoassay of its products which would detect 10”‘ mol of 2-5A cores. Although cells of both sublines fully differentiate (as measured by benzidine staining), only in one subline was there an increase in 2-5A synthetase activity upon treatment with Me2S0. Hexamethylenebisacetamide, another potent agent of differentiation in this system, did not increase 2-5A synthetase activity in either of these two sublines. An IFNresistant FLC variant differentiated normally upon treatment with M e 8 0 or hexamethylenebisacetamide while it was noninducible for 2-5A synthetase activity by exogenous IFN or by the inducers themselves. A similar situation has been observed with regard to the level of phosphorylation of the IFN-induced M, = 67,000 protein band. In addition, treatment of IFNsensitive and resistant FLC sublines with mouse &IFN antiserum did not affect differentiation. Even though we have duplicated previous findings on the increase of 2-5A synthetase activity in MeaSO-induced FLC, the lack of any such increase with other inducers or other sublines indicates that there is no causal relationship between the enzyme activation and FLC differentiation.

Bromodeoxyuridine resistance: thymidine transport and phosphorylation in Friend leukemia cells

Abstract: We have studied multiple step bromodeoxyuridine (BrdU) resistance in Friend leukemia cells. The mutation rate to 30 micrograms/ml resistance was 5.1 X 10(-5) per cell per generation, and to 100 micrograms/ml was 3.7 X 10(-7) per cell per generation. Resistant variants could not be obtained in a single step using BrdU concentrations higher than 100 micrograms/ml. Three clones isolated through multiple step selection were resistant to 640 micrograms/ml of BrdU and deficient in thymidine kinase, although their ability to transport radiolabeled thymidine was unimpaired relative to wild type. All three clones had low reversion frequencies, as judged by plating efficiencies in couterselective HAT medium. Two such revertant clones were isolated and tested for their forward mutation frequency in BrdU. No resistant clones were obtained when as many as 5 X 10(7) cells were tested. This observation argues against the hypothesis that the Friend cells possess two functional thymidine kinase loci and that the revertants represent a heterozygous condition. We conclude that the hypothesis of null mutations within a hemizygous or heterozygous thymidine kinase locus is sufficient to account for high-level BrdU resistance in Friend leukemia cells.

Dimethyl Sulfoxide-Induced Inhibition of the Immunosuppressive Activity of Cultured Friend Erythroleukemia Cells

Abstract: Two Friend leukemia virus-induced tumor cell lines lost their immunosuppressive properties in vitro when treated with dimethyl sulfoxide (DMSO), a known cellular differentiation agent. Incubation of the cell lines, GM 979 and GM 86, with DMSO for 4 days or longer, inhibited their ability to suppress the antibody forming capacity of normal murine spleen cells immunized in vitro with sheep red blood cells. Suppression of the inhibitory capability of the tumor cell lines by DMSO was time dependent. Three days incubation caused only slight, if any, inhibition, while a shorter period of treatment had no effect. Inhibition of the immunosuppressive properties of the tumor cell lines was not due to a decrease in tumor cell viability. The development of previously reported metabolic alterations in the treated cells, such as increased hemoglobin synthesis and other physicochemical alterations, paralleled cellular differentiation, and loss of immunosuppressive properties.