Minoo Battiwalla, Yiyuan Wu, Rajinder P. S

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Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis Minoo Battiwalla, Yiyuan Wu, Rajinder P.S. Bajwa, Marija Radovic, Nikolaos G. Almyroudis, Brahm H. Segal, Paul K. Wallace, Ryotaro Nakamura, Swaminathan Padmanabhan, Theresa Hahn, Philip L. McCarthy Biology of Blood and Marrow Transplantation Volume 13, Issue 7, Pages 765-770 (July 2007) DOI: 10.1016/j.bbmt.2007.03.009 Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 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. Biology of Blood and Marrow Transplantation 2007 13, 765-770DOI: (10.1016/j.bbmt.2007.03.009) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 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. Biology of Blood and Marrow Transplantation 2007 13, 765-770DOI: (10.1016/j.bbmt.2007.03.009) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 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). Biology of Blood and Marrow Transplantation 2007 13, 765-770DOI: (10.1016/j.bbmt.2007.03.009) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions