Biological Consequences of Guanine Starvation

Sadée, Wolfgang; Nguyen, Binh

doi:10.1007/978-1-4613-2449-2_14

Genetic Consequences of Nucleotide Pool Imbalance 1985

DOI: 10.1007/978-1-4613-2449-2_14

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Biological Consequences of Guanine Starvation

Wolfgang Sadée

Binh Nguyen

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1994

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“…Because lymphoid cells cannot use the salvage pathway for purine synthesis (3), depletion of dGTP inhibits DNA replication (6,21). MPA was shown to inhibit proliferation of B and T lymphocytes in vitro and in vivo (2,(7)(8)(9).…”

mentioning

confidence: 99%

Effect of mycophenolic acid on Epstein-Barr virus infection of human B lymphocytes

Alfieri

Allison

Kieff

1994

Antimicrob Agents Chemother

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minute, with a Betaplate scintillation counter (Pharmacia LKB Biotechnology Inc., Piscataway, N.J.). By 3 days postinfection, large cell clumps were evident only in cultures exposed to MPA concentrations of less than 1.0 ,uM, a concentration which inhibited thymidine uptake in both EBV-infected and uninfected cells ( Fig. 1; see below).Indirect immunofluorescence microscopy was performed 4 days after primary B-lymphocyte infection, with monoclonal antibodies PE2 and CS1-4 (27) (donated by L. Young and A. Rickinson, Birmingham, England), which are reactive to EBV nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1), respectively. A goat anti-mouse secondary antibody conjugated to fluorescein isothiocyanate (Jackson ImmunoResearch Laboratories Inc., West Grove, Pa.) was added in a secondary step. The results in Table 1 indicate that 2 to 5% and 1 to 2% of the cells expressed EBNA-2 and LMP-1, respectively, following a single round of cell division. This expression of EBNA-2 and LMP-1 was not affected by an MPA concentration of 0.1 or 0.01 ,uM. However, 1.0 ,uM MPA inhibited, but did not completely block, EBNA-2 and LMP-1 expression, thereby reducing the number of EBNA-2-and LMP-1-expressing cells to 1% or less. At concentrations higher than 1.0 ,uM MPA, no further reduction in EBNA-2 and LMP-1 expression was noted, indicating that even high concentrations of MPA could not completely block EBNA-2 and LMP-1 expression. A 50% reduction of EBNA-2 and LMP-1 fluorescence might be expected because of a nonspecific antiproliferative effect of MPA (see below), since the first round of cell division after EBV infection of B lymphocytes in vitro is between 36 and 72 h postinfection (1,19,25). Since both EBNA-2 and LMP-1 are putative mediators of EBV-induced B-cell transformation (12), the inability of MPA to inhibit their expression completely might indicate that MPA cannot prevent initiation of the transforming process.MPA concentrations of 1.0 ,uM and above inhibited the outgrowth of EBV-transformed cells (Fig. 1). However, even this was likely due to an antiproliferative effect of MPA rather than an effect on EBV initiation or maintenance of transformation, since reversibility studies showed that treatment with 2.5 ,uM MPA from the time of infection to 5 days

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mentioning

confidence: 99%

Effect of mycophenolic acid on Epstein-Barr virus infection of human B lymphocytes

Alfieri

Allison

Kieff

1994

Antimicrob Agents Chemother

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Biological Consequences of Guanine Starvation

Cited by 1 publication

References 4 publications

Effect of mycophenolic acid on Epstein-Barr virus infection of human B lymphocytes

Effect of mycophenolic acid on Epstein-Barr virus infection of human B lymphocytes

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