Inhibition of cell division by interferons. The relationship between changes in utilization of thymidine for DNA synthesis and control of proliferation in Daudi cells

Gewert, Dirk R.; Moore, Graham; Clemens, M J

doi:10.1042/bj2140983

Cited by 49 publications

(30 citation statements)

References 35 publications

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“…]leucine (New England Nuclear) was measured by trichloroacetic acid precipitation of protein as described previously [11,12,16,18]. The concentrations and specific radioactivities of these precursors are given in the legends.…”

Section: Cell Culturementioning

confidence: 99%

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

McNurlan¹,

Clemens²

1986

Biochemical Journal

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Treatment of the Daudi line of human lymphoblastoid cells with concentrations of human interferons within the physiological range progressively inhibits cell proliferation over 1-4 days. Rigorous measurement of the overall rate of protein synthesis during this period, using a concentration of [3H]phenylalanine sufficient to equalize the specific radioactivity of intracellular and extracellular precursor pools, shows that protein synthesis becomes progressively inhibited as the growth inhibition develops. There is a strong correlation between inhibition of amino acid incorporation and inhibition of cell proliferation. In contrast, we find no evidence for any increase in protein degradation rate under these conditions. These results suggest that interferon treatment of susceptible cells can inhibit protein synthesis even in the absence of virus infection and that this inhibition is of a sufficient magnitude to account for the anti-proliferative effect. INTRODUCTIONThe ability of interferons to inhibit viral replication in infected cells through effects on [4][5][6]. On the other hand,-inhibition of incorporation of labelled amino acids has been observed in some systems in which cell proliferation is inhibited [7][8][9]. The human lymphoblastoid Daudi cell line is extremely sensitive in exhibiting a marked suppression of growth when human interferons are added in culture [10][11][12]. We have investigated, using this system, the extent to which the changes in growth rate can be correlated with changes in protein synthesis. In order to do this it is necessary to quantify both processes rigorously. Such an approach also allows indirect estimates to be made of the rate of protein breakdown, and of the relative contributions of changes in synthesis versus breakdown to the inhibition of cell growth caused by interferon treatment.The rate of incorporation of a radioactive amino acid into protein reflects both the actual rate at which protein is synthesized and the specific radioactivity of the precursor which is being incorporated. If the values of the latter are different between two populations of cells then spurious conclusions can be drawn. In an attempt to overcome any such problems we have adapted procedures developed for measurement of protein synthesis rates in perfused organs [13] and in tissues of

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Section: Cell Culturementioning

confidence: 99%

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

McNurlan¹,

Clemens²

1986

Biochemical Journal

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“…We have examined the effects of anti-IgM on various B lymphocyte cell lines, particularly B lymphoblastoid cell lines (8 -10). These results show that anti-IgM induces apoptosis in EBV 1 -negative cell lines (including Ramos and ST486), but induces growth arrest without apoptosis in EBV-positive cell lines (including Daudi and Raji) (this report) (11)(12)(13). This in turn led us to examine in greater detail the molecular events which may precede anti-IgM-mediated induction of apoptosis in Ramos.…”

mentioning

confidence: 99%

Anti-IgM-mediated Regulation of c-myc and Its Possible Relationship to Apoptosis

Kaptein¹,

Lin²,

Wang³

et al. 1996

Journal of Biological Chemistry

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“…Initially, the direct cytostatic effect of IFN-a was thought to be the major mechanism by which it inhibits tumor growth (33,34,48); however, subsequent studies revealed that inhibition of angiogenesis and induction of tumor cell apoptosis are other IFN-a mediated antitumor effects (7,10,(49)(50)(51)(52). Our in vitro studies revealed that B16F10 melanoma cells are more sensitive to the cytostatic effects of IFN-a, whereas the CT26 colon carcinoma cells are more sensitive to the proapoptotic properties of rmIFN-a in vitro.…”

Section: Discussionmentioning

confidence: 99%

Administration of IFN-α Enhances the Efficacy of a Granulocyte Macrophage Colony Stimulating Factor–Secreting Tumor Cell Vaccine

Prell

Li²,

Lin³

et al. 2005

Cancer Research

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IFN-A is approved for the treatment of multiple cancers. Its pleiotropic properties include inhibition of proliferation and angiogenesis and induction of apoptosis. Type I IFNs also exert immunomodulatory effects, which make it an appropriate candidate to combine with cancer vaccines. The studies reported herein show that 50% of mice reject established B16 tumors following treatment with the combination of a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine (B16.GM) and subclinical doses of recombinant murine IFN-A delivered at the vaccine site. Similarly, 80% of mice treated with the combination reject established B16 tumors when recombinant murine IFN-A is given at the challenge site, suggesting that in the latter case its antiproliferative, proapoptotic, and antiangiogenic properties may be involved in controlling tumor growth. In contrast, fewer than 10% of mice reject the tumors when either one is used as a monotherapy. Furthermore, a 30-fold increase in the frequency of melanoma-associated antigen (Trp-2 and gp100) specific T cells was observed in mice treated with the combination when compared with unvaccinated controls. These data show that IFN-A combined with a granulocyte macrophage colonystimulating factor-secreting tumor cell vaccine significantly enhances vaccine potency and may represent a potential new approach for tumor immunotherapy. (Cancer Res 2005; 65(6): 2449-56)

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Inhibition of cell division by interferons. The relationship between changes in utilization of thymidine for DNA synthesis and control of proliferation in Daudi cells

Cited by 49 publications

References 35 publications

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

Anti-IgM-mediated Regulation of c-myc and Its Possible Relationship to Apoptosis

Administration of IFN-α Enhances the Efficacy of a Granulocyte Macrophage Colony Stimulating Factor–Secreting Tumor Cell Vaccine

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