Showing papers on "Friend leukemia published in 1977"

Tumor neutralization, immunotherapy, and chemoimmunotherapy of a friend leukemia with cells secondarily sensitized in vitro.

Abstract: The aim of our study was to induce in vitro a secondary response to a C57BL/6 Friend leukemia (FBL-3) by C57BL/6 lymphoid cells, to document their enhanced anti-tumor cytotoxicity in vitro and to study their anti-tumor effect in vivo by tumor neutralization (Winn assay) and tumor therapy of progressive FBL-3 in C57BL/6 mice. Spleen cells (Ci) from mice immunized once in vivo with FBL-3 were cultured for 5 days with either x-irradiated FBL-3 (CiFx), C57BL/6 spleen cells (CiCx), BALB/c spleen cells (CiBx) or without any x-irradiated cells (Ci-cult.) and their activity subsequently was assayed in vitro and in vivo . CiFx cells were markedly more cytotoxic in vitro by the 51 Cr release assay than were CiCx or CiBx and were most effective in tumor neutralization (Winn assay). For adoptive immunotherapy, mice given lethal (10 4 ) FBL-3 i.p. on day 0 received the cultured spleen cells on day 1. Treatment with 5 × 10 6 CiFx cured 14 of 14 mice whereas 19 of 20 mice given 5 × 10 6 CiCx or CiBx died with tumor. For adoptive chemoimmunotherapy of advanced leukemia, mice were given 10 7 FBL-3 i.p. on day 0. On day 5, they received cyclophosphamide (CY) plus cultured spleen cells. Untreated mice died by day 14. CY alone prolonged survival but all mice died within 4 weeks. Treatment with CY plus 5 × 10 6 Ci-cult. or CiBx was no more effective than CY alone—40 of 40 mice died with tumor. However, CY plus 5 × 10 6 CiFx cured 16 of 22 mice. Thus, cells generated in a secondary response in vitro were not only cytotoxic in vitro and effective in tumor neutralization, but were also curative in immunotherapy of an early leukemia and in chemoimmunotherapy of an advanced leukemia.

Effect of interferon on growth and division cycle of Friend erythroleukemic murine cells in vitro.

Abstract: The administration of appropriate doses of interferon to cultures of Friend leukemia cells causes a pronounced inhibition of cell growth. Several lines of evidence indicate that this effect is due to interferon itself, rather than to unknown contaminants of interferon preparations. Autoradiograph analysis of growth parameters of Friend leukemia cells during treatment with interferon demonstrates that the rate of entry into the S phase, the percent decline of unlabeled mitoses, and the mitotic indexes are significantly lower in interferon-treated cell cultures than in control untreated cultures when tritiated thymidine was added 12 h after the administration of interferon. These data indicate that fractions of interferon-treated cell population are delayed in both G1 and in G2 phases of the cell cycle. This was confirmed by exact measurements of the length of the various phases of the cycle. The interferon-induced inhibition of growth of Friend leukemia cells is reversible after removal of the compound. Autoradiograph data obtained from control cultures and from cultures previously treated with interferon that had been washed free of interferon and reseeded in interferon-free medium, demonstrate that during the first 12 h after removal of interferon, a large majority of the cells previously treated with interferon had a deranged flow into the S phase, a high number of unlabeled mitoses, and a low mitotic index. These data provide further evidence for the above-mentioned prolongations of G1 and G2 phases of the cell cycle. All growth parameters tested reverted to normal values within 12 h after washing out interferon.

Biochemical and immunological characterization of two distinct variants of histone H2A in Friend leukemia

Abstract: Changes in the relative amount of two histone H2A subfractions have been observed in cells at different proliferative stages of Friend leukemia. Biochemical analyses of the purified H2A subfractions reveal them to be different in primary structure, and not the result of postsynthetic modifications of the same parent protein. Antibodies raised against the purified H2A.2 subfraction cross react with H2A.1 and H2A.2, but show high specificity for the immunizing subfraction at higher sera dilutions. Only H2A.2 contains a methionine which appears critical to an antigenic difference that immunologically distinguishes H2A.2 from H2A.1. The observed change in the relative amounts of two nonallelic variants of a histone coincident with changes in the physiologic states of the cell may indicate a correlation between genome structure and function.

Localization of the globin gene in the template active fraction of chromatin of Friend leukemia cells.

Abstract: Friend leukemia cell chromatin has been fractionated into template active and inactive components. The globin gene sequence is associated with the template active component both prior to and after the cells are induced with dimethyl sulfoxide to synthesize hemoglobin and therefore appears to be in an active configuration in uninduced as well as in induced Friend leukemia cells. In cells which have lost the ability to produce hemoglobin, the globin gene sequence is not associated with the template active fraction of chromatin. These results demonstrate the success of the fractionation procedure.

Induction of globin gene expression in cultured erythroleukemia cells by butyric acid.

Abstract: Butyric acid induces erythroid differentiation of cultured Friend leukemia cells when added to the culture medium. A high level of globin messenger RNA (mRNA) was detected in Friend leukemia cells treated with butyric acid by a liquid hybridization method using radioactive DNA complementary to reticulocyte globin mRNA. The content of globin mRNA molecules induced in the cytoplasm of the butyric acid-treated Friend leukemia cells paralleled the hemoglobin content determined by the benzidine staining method. Therefore, this hemoglobin synthesis may be most reasonably explained in terms of transcriptional activation of globin genes, as previously proposed in the case of dimethylsulfoxide, another inducer of erythroid differentiation. Induced accumulation of globin mRNA in the nuclei also supports this interpretation.

Amino Acid Control of Stable RNA Synthesis in Friend Leukemia Cells in Relation to Intracellular Purine Nucleoside Triphosphate Levels

Abstract: Histidinol is known to cause deacylation of histidyl-tRNA in cultured mammalian cells, thereby producing a functional deprivation of histidine. Such deprivation of an essential amino acid is known to produce various effects, including inhibition of tRNA synthesis and of nucleolar RNA synthesis and processing. It has been proposed [Grummt, F. & Grummt, I. (1976) Eur. J. Biochem. 64, 307-312] that this response to amino acid deprivation is mediated by decreases in GTP and ATP pool sizes caused by a deacylated-tRNA-dependent hydrolysis of GTP. In contrast, we find that Friend leukemia cells treated with histidinol show no significant changes in GTP or ATP pool sizes, although this treatment does produce the expected inhibition of rRNA and tRNA synthesis.

Effect of the nitrosourea derivative rpcnu (ICIG 1163) on the development of Friend leukemia in mice.

Abstract: Friend leukemia was used as an experimental model to study the action of a ribofuranosyl derivative of nitrosourea : RPCNU. This new product was known to be active in L 1210 leukemia and immunosuppressive. RPCNU significantly decreases the splenomegaly induced in DBA2 mice by Friend virus when it is given at a time ranging from 7 days before to 14 days after virus inoculation. The survival time in leukemic treated groups is also greatly increased. However, viral content of the spleen extracts of the leukemic treated mice is not reduced. Therefore, RPCNU cannot be considered as an antiviral agent. A comparison between survival of leukemic and non leukemic mice treated with different doses show that the effectiveness of RPCNU is correlated with its toxicity. The effect of RPCNU on Friend leukemia by cytotoxicity on hematopoietic stem cells is discussed in this paper.

Viral Reverse Transcriptase Suppression Associated With Erythroid Differentiation of Friend Leukemia Cells

Abstract: The Friend erythroleukemia cell line T3-C12, which produces Friend murine leukemia virus (F-MuLV) and can be induced to synthesize hemoglobin by dimethyl sulfoxide (DMSO), was monitored for viral RNA-dependent DNA polymerase reverse transcriptase (RT) activity. The amount of viral 60-70S RNA released from DMSO-treated cells was unaffected or increased compared to that from control cells, while RT activity from treated cells was decreased. Accordingly, the specific activity in F-MuLV from DMSO-treated cells expressed as RT/70S RNA was decreased to 8% of the control activity. The 5-bromo-2'-deoxyuridine added to cultures containing DMSO reversed the differentiation process, and the F-MuLV thus treated did not exhibit the reduced RT activity normally observed in DMSO-treated virus. Cell-free F-MuLV incubated with and without DMSO showed the same RT activity, indicating that DMSO itself did not inhibit RT activity. However, when F-MuLV-containing pellets from control and DMSO-treated culture fluids were mixed, there was marked inhibition of the control RT activity, suggesting that RNase hybrid activity was stimulated or that an inhibitor was produced. Assays of F-MuLV-RNase hybrid released from control and DMSO-treated cells showed no difference in activity, indicating that a specific inhibitor of RT was produced or activated. Additions of certain nucleotide triphosphates to RT incubation mixtures did not result in any stimulation of RT activity in DMSO-treated F-MuLV, suggesting that phosphatase was not responsible for the observed inhibition. The results suggested that DMSO treatment of T3-C12 cells caused a reduction in viral RT activity by stimulating the production of an inhibitor, the nature of which is unknown.

Role of Friend-associated lymphatic leukemia virus in immunization against Friend leukemia complex

Abstract: Mice inoculated with Friend leukemia complex (FLC) pretreated with concanavalin A are resistant to FLC challenge only when they have become infected with the FLC-associated lymphatic leukemia virus (LLV). In interpreting states of resistance to FLC induced by various immunizing procedures, the possibility that immunity is sustained by an unrecognized LLV infection should always be considered.