Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis

Effect of ganciclovir, foscarnet, and tacrolimus on 3H incorporation in normal human PBMCs stimulated with PHA (A) or CMV antigen (B). Values are medians; error bars represent SEM. The stimulation index (SI) was determined by dividing the average of the experimental results of each quadruplicate by the average of the unstimulated cells on the same plate.

Effect of ganciclovir on apoptosis. Raji cell line with media alone, ganciclovir, or HD10 (A,B). Normal human PBMCs either resting or stimulated by PHA or EBV-antigen with varying concentrations of ganciclovir (C). Values are medians; error bars represent SEM.

Normal human PBMCs in RPMI-CM 10% AB-serum were exposed to ganciclovir (30 μg/mL) for 1, 3, or 4 days followed by 30 minutes of BrdU exposure. Anti-BrdU-FITC antibody and 7-AAD were used to determine the stage in the cell cycle. A lymphocyte gate was applied on the basis of FSC and SSC. FL3-W versus FL3-A doublet discrimination was applied. BrdU incorporation was measured by flow cytometry after application of a lymphogate by FSC/SSC properties and elimination of doublet cells. The proportion of cells in apoptosis, G0/G1, S-phase, and G2/M are shown in these representative panels (A). The median percentages ± SEM for cells in cycle (G2+S) or S-phase alone under various conditions are shown (B).