Immunosuppressive effects of methylglyoxal-bis(guanylhydrazone) on mouse bone marrow and spleen cells and their antagonism by spermidine

Bennett, James A.; Ehrke, J; Fadale, Paul D.; Dave, C.; Mihich, Enrico

doi:10.1016/0006-2952(78)90485-9

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…KG-1a cells (1×10 5 cells/mL, 3×T75 flasks, 50 mL/flask) were incubated with 0.3 µM [ 14 C]-AZA for 24 hours. Radioactive measurement of the trichloroacetic acid (TCA)-precipitable fraction, representing total nucleic acid (RNA + DNA), was performed as previously described [25], [26]. Alkali-stable, TCA-precipitable radioactivity is a measure of the incorporation of nucleosides into DNA.…”

Section: Methodsmentioning

confidence: 99%

A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines

Hollenbach¹,

Nguyen²,

Brady³

et al. 2010

PLoS ONE

324

310

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BackgroundThe cytidine nucleoside analogs azacitidine (AZA) and decitabine (DAC) are used for the treatment of patients with myelodysplastic syndromes and acute myeloid leukemia (AML). Few non-clinical studies have directly compared the mechanisms of action of these agents in a head-to-head fashion, and the agents are often viewed as mechanistically similar DNA hypomethylating agents. To better understand the similarities and differences in mechanisms of these drugs, we compared their in vitro effects on several end points in human AML cell lines.Methodology/Principal FindingsBoth drugs effected DNA methyltransferase 1 depletion, DNA hypomethylation, and DNA damage induction, with DAC showing equivalent activity at concentrations 2- to 10-fold lower than AZA. At concentrations above 1 µM, AZA had a greater effect than DAC on reducing cell viability. Both drugs increased the sub-G1 fraction and apoptosis markers, with AZA decreasing all cell cycle phases and DAC causing an increase in G2-M. Total protein synthesis was reduced only by AZA, and drug-modulated gene expression profiles were largely non-overlapping.Conclusions/SignificanceThese data demonstrate shared mechanisms of action of AZA and DAC on DNA-mediated markers of activity, but distinctly different effects in their actions on cell viability, protein synthesis, cell cycle, and gene expression. The differential effects of AZA may be mediated by RNA incorporation, as the distribution of AZA in nucleic acid of KG-1a cells was 65∶35, RNA∶DNA.

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Section: Methodsmentioning

confidence: 99%

A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines

Hollenbach¹,

Nguyen²,

Brady³

et al. 2010

PLoS ONE

324

310

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“…Mice treated with BCG (Tice strain, University of Illinois) were given 2 X 107 viable units intravenously. Bone marrow cells (from the femur and tibia) and spleen cells were obtained and suspended under sterile conditions as previously described (10). Immunization in vitro was carried out according to a modification of the procedure of Mishell and Dutton (11).…”

Section: Methodsmentioning

confidence: 99%

“…C57BL/6 (H-2b) female mice, [6][7][8][9][10] weeks old, were obtained from Charles River Laboratories (Wilmington, MA). Mice treated with BCG (Tice strain, University of Illinois) were given 2 X 107 viable units intravenously.…”

Section: Methodsmentioning

confidence: 99%

Systemic bacillus Calmette-Guérin (BCG) activates natural suppressor cells.

Bennett¹,

Rao²,

Mitchell³

1978

Proc. Natl. Acad. Sci. U.S.A.

103

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Addition of normal C57BL/6 mouse bone marrow cells to an in vitro culture of normal C57BL/6 spleen cells and allogeneic P815-Y tumor cells inhibited the development of cell-mediated immunity. Bacillus Calmette-Guérin (BCG) enhanced the suppressive activity of these bone marrow cells as early as 2 days after its intravenous administration to donor mice and elicited similar activity in the spleen by 7 days. Concomitant with the appearance of suppressor cells in the spleen there was a decrease in bone cell number and an increase in spleen cell number. While normal spleen cells failed to inhibit immunization, spleen cells from thymectomized, irradiated, bone marrow-reconstituted mice were inhibitory. Administration of BCG further increased the suppressive activity of spleen cells in these T cell-deprived mice. From this evidence it appears that systemic administration of BCG activates natural suppressor cells in the bone marrow and elicits suppressor cells in the spleen through the migration and colonization of the spleen by bone marrow elements.

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Induction of suppressor cells by intravenous administration of Bacillus calmette-guérin and its modulation by cyclophosphamide

Bennett

Mitchell

1979

Biochemical Pharmacology

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Immunosuppressive effects of methylglyoxal-bis(guanylhydrazone) on mouse bone marrow and spleen cells and their antagonism by spermidine

Cited by 5 publications

References 14 publications

A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines

A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines

Systemic bacillus Calmette-Guérin (BCG) activates natural suppressor cells.

Induction of suppressor cells by intravenous administration of Bacillus calmette-guérin and its modulation by cyclophosphamide

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