Studies on in vitro lymphocyte proliferation in cultures synchronized by the inhibition of DNA synthesis

1970 ◽  
Vol 61 (2-3) ◽  
pp. 333-341 ◽  
Author(s):  
Janina Jasińska ◽  
J.A. Steffen ◽  
A. Michałowski
Keyword(s):  
Dna Synthesis ◽  
Lymphocyte Proliferation ◽  
Inhibition Of Dna Synthesis

Potentiation of the bleomycin, arabinofuranosylcytosine and adriamycin-caused inhibition of DNA synthesis in lymphocytes by bestatin in vitro

1985 ◽  
Vol 21 (11) ◽  
pp. 1325-1330 ◽  
Author(s):  
G. Leyhausen ◽  
H.C. Schröder ◽  
D.K. Schuster ◽  
A. Maidhof ◽  
H. Umezawa ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Inhibition Of Dna Synthesis

Inhibition of DNA synthesis in vitro by binding of benzo(a)pyrene metabolite diol-epoxide I to DNA

Nature ◽  
1979 ◽  
Vol 279 (5708) ◽  
pp. 75-78 ◽  
Author(s):  
HIROSHI MIZUSAWA ◽  
TSUYOSHI KAKEFUDA
Keyword(s):  
Dna Synthesis ◽  
Diol Epoxide ◽  
Inhibition Of Dna Synthesis

Ganciclovir Suppresses Human T Lymphocyte Proliferation In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5378-5378
Author(s):  
Minoo Battiwalla ◽  
Yiyuan Wu ◽  
Ryotaro Nakamura ◽  
Marija Radovic ◽  
Rajinder P.S. Bajwa ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
T Lymphocyte ◽  
Lymphocyte Proliferation ◽  
Brdu Incorporation ◽  
Human Pbmcs ◽  
Post Transplant ◽  
T Lymphocyte Proliferation ◽  
Proliferation In Vitro ◽  
Cmv Reactivation

Abstract Clinically significant cytomegalovirus (CMV) infection in allogeneic blood or marrow transplant recipients has dramatically declined in recent years by the strategy of early detection of reactivation and pre-emptive therapy with Ganciclovir (GCV). We have previously shown that even in the absence of overt CMV disease, persisting post-transplant antigenemia predicts for increased late relapse and treatment failure. (Nakamura, et al BBMT 2004) In other words, frequent CMV reactivation serves as a surrogate for impaired post-transplant immune reconstitution. To explain the observed association between CMV reactivation and relapse we also raised the possibility that several weeks of GCV therapy could exert a deleterious effect on a fragile immune system. Clinical association between GCV administration and impaired lymphocyte function has not received attention previously; perhaps because of confounding effects from the underlying conditions (HIV or post-transplant) that induce CMV reactivation. We examined the effect of GCV in vitro on normal human PBMCs. Human PBMCs were extracted from normal volunteers and subjected to mitogenic stimulation (PHA) in the absence or presence of varying concentrations of GCV. PHA-induced proliferation, measured by uptake of 3[H]-thymidine after 5 days incubation in RPMI-10% AB serum, was reduced by 35% at peak therapeutic concentrations (10mg/ml) of GCV as opposed to 73% by Tacrolimus (10ng/ml). GCV did not induce lymphocyte apoptosis in the presence or absence of stimulation. Flow cytometry-based BrdU incorporation assays show that GCV exerts a time-dependent impairment of DNA synthesis in lymphocytes. Collectively, these results show that GCV suppresses T-lymphocyte proliferation in vitro at therapeutic concentrations and the likely mechanism of action is inhibition of DNA synthesis. Further work is ongoing to evaluate the effect of GCV on proliferative responses to specific antigens and to confirm these effects in comparison to other drugs used in the transplant setting. Figure Figure

scholarly journals The inhibition of nucleic acid synthesis by mycophenolic acid

1969 ◽  
Vol 113 (3) ◽  
pp. 515-524 ◽  
Author(s):  
T J Franklin ◽  
Jennifer M. Cook
Keyword(s):  
Dna Synthesis ◽  
Mycophenolic Acid ◽  
Early Stage ◽  
Acid Synthesis ◽  
Purine Nucleotides ◽  
Free System ◽  
L Cells ◽  
A Cell ◽  
Inhibition Of Dna Synthesis

1. Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro. 2. The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [14C]thymidine. 3. The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine. 4. The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine. 5. Mycophenolic acid does not inhibit the incorporation of [14C]thymidine into DNA in suspensions of Landschütz and Yoshida ascites cells in vitro. 6. Mycophenolic acid inhibits the conversion of [14C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschütz and Yoshida ascites cells and also in L cells in vitro. There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic. 7. Mycophenolic acid inhibits the conversion of [14C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschütz cells capable of converting hypoxanthine into IMP, XMP and GMP. 8. Preparations of IMP dehydrogenase from Landschütz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid. The inhibition showed mixed type kinetics with Ki values of between 3·03×10−8 and 4·5×10−8m. 9. Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschütz and Yoshida ascites cells and L cells in vitro.

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