In vitro and in vivo toxicity of 2′,3′-dideoxycytidine in mice

Rossi, Luigia; Brandi, Giorgio; Schiavano, Giuditta Fiorella; Chiarantini, Laura; Albano, A; Magnani, Mauro

doi:10.1016/0009-2797(92)90066-t

Cited by 16 publications

(4 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that ddC phosphorylating enzymes (dCK) in human and mouse cells have significantly different substrate specificity (Habteyesus et al, 1991). The differences in ddC substrate specificity may be responsible for the inability of 100 µM ddC to inhibit cell growth in mouse myeloma cells (Rossi et al, 1992) and for its inability to deplete the mtDNA of the mouse cells in our experiment (lanes 3 and 4 in Fig. 2).…”

Section: Treatment With Etbr and Ddc Decrease The Mtdna Contentmentioning

confidence: 68%

Rapid Isolation of Mitochondrial DNA-Depleted Mammalian Cells by Ethidium Bromide and Dideoxycytidine Treatments

Yoon¹,

Oh²,

Yoo³

2014

Journal of Applied Biological Chemistry

View full text Add to dashboard Cite

Mitochondrial DNA (mtDNA)-depleted (ρ 0) cells are often used as mtDNA recipients to study the interaction between the nucleus and mitochondria in mammalian cells. Therefore, it is crucial to obtain mtDNA-depleted cells with many different nuclear backgrounds for the study. Here, we demonstrate a rapid and reliable method to isolate mammalian mtDNA-depleted cells involving treatment with the antimitochondrial agents ethidium bromide (EtBr) and 2',3'-dideoxycytidine (ddC). After a short exposure to EtBr or ddC, followed by rapid clonal isolation, we were able to generate viable mtDNA-depleted cells from mouse and human cells and were able to successfully repopulate them with exogenous mitochondria from platelets isolated from mouse and human blood samples. These mtDNA-depleted cells can be used to characterize the nuclear mitochondrial interactions and to study mtDNA-associated defects in mammalian cells. Our method of isolating mtDNA-depleted cells is practical and applicable to a variety of cell types.

show abstract

Section: Treatment With Etbr and Ddc Decrease The Mtdna Contentmentioning

confidence: 68%

Rapid Isolation of Mitochondrial DNA-Depleted Mammalian Cells by Ethidium Bromide and Dideoxycytidine Treatments

Yoon¹,

Oh²,

Yoo³

2014

Journal of Applied Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Murine cells have been reported to be less sensitive to ddC as a result of limited phosphorylation (Balzarini et al, 1988;Rossi et al, 1992 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of HIV-1 and LP-BM5 Replication in Macrophages by Dideoxycytidine and Dideoxycytidine 5′-Triphosphate

Magnani

Casabianca

Rossi

et al. 1995

Antivir Chem Chemother

View full text Add to dashboard Cite

The antiviral agent 2′,3′-dideoxycytidine (ddC) has been shown to be active against HIV-1 infectivity. However, conflicting results have been reported concerning its efficacy in macrophages. Because macrophages possess low levels of the kinase(s) responsible for ddC phosphorylation, we investigated the ability of ddC and 2′,3′-dideoxycytidine 5′-trisphosphate (ddCTP) to suppress HIV-1 and LP-BM5 replication in these cells. Retrovirus replication was only partially inhibited in the two systems investigated by a high (1 μM) ddC concentration. The direct administration of ddCTP, using autologous red blood cells as a delivery system, was found to inhibit HIV-1 and LP-BM5 replication by more than 90% in macrophages without affecting major cell functions. These data, together with those already reported for FIV [Magnani et al. (1994) AIDS Res Hum Retroviruses 10: 1179-1186], suggest that the anabolic phosphorylation of ddC is an important determinant of its anti-HIV activity and that pharmacological interventions that modulate ddC metabolism may be useful for improving its antiretroviral activity in macrophages.

show abstract

“…Lymphocyte proliferative index 3 [H] Thymidine incorporation upon lymphocyte stimulation by phytohemagglutinin (PHA) for T cells and lipopolysaccharide (LPS) for B cells was measured as previously described [11].…”

Section: Competitive Polymerase Chain Reaction Analysis Of Lp±bm5 Promentioning

confidence: 99%

New drug combinations for the treatment of murine AIDS and macrophage protection

Fraternale

Casabianca

Tonelli

et al. 2001

Eur J Clin Investigation

View full text Add to dashboard Cite

The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macrophages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of the lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) encapsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus GSH-loaded erythrocytes given with AZT (treatment A + L-RBC). Fludarabine was administered intraperitoneally, AZT in the drinking water and GSH was encapsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. The results obtained show that GSH-loaded erythrocytes provide additive effects in all the parameters examined. Alternation of a lympholitic drug and antiretroviral drug is effective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting different infectable cell compartments are better than treatments protecting mainly lymphocytes.

show abstract

In vitro and in vivo toxicity of 2′,3′-dideoxycytidine in mice

Cited by 16 publications

References 22 publications

Rapid Isolation of Mitochondrial DNA-Depleted Mammalian Cells by Ethidium Bromide and Dideoxycytidine Treatments

Rapid Isolation of Mitochondrial DNA-Depleted Mammalian Cells by Ethidium Bromide and Dideoxycytidine Treatments

Inhibition of HIV-1 and LP-BM5 Replication in Macrophages by Dideoxycytidine and Dideoxycytidine 5′-Triphosphate

New drug combinations for the treatment of murine AIDS and macrophage protection

Contact Info

Product

Resources

About