PMID: 9191020May 1, 1997Paper

Lack of mitochondrial toxicity in CEM cells treated with carbovir

Antiviral Research
W B ParkerL L Bennett

Abstract

Carbovir (CBV) is a guanine nucleoside analog with potent in vitro anti-HIV activity. A prodrug of CBV is currently being evaluated in clinical trials as a potential agent for the treatment of AIDS. The ability of CBV to inhibit mitochondrial DNA synthesis in intact CEM cells was evaluated in the present study, because most of the currently available anti-HIV nucleoside analogs have significant toxicities that result from their inhibition of mitochondrial DNA synthesis. No delayed cytotoxicity was observed in CEM cells treated with 50 microM CBV for 4 weeks. In addition, CBV at concentrations as high as 1 mM did not cause a decline in mitochondrial DNA levels and only minimally increased the concentration of lactic acid in the medium. In contrast to these results with CBV, treatment of CEM cells with 0.5 microM 2',3'-dideoxycytidine resulted in delayed cytotoxicity, a decrease in mitochondrial DNA content and increases in lactic acid levels in the medium. These results indicated that treatment of CEM cells with CBV did not result in the inhibition of mitochondrial DNA synthesis and suggested that treatment of AIDS patients with CBV, or a prodrug of CBV, would not result in some of the toxicities seen with the other anti-HIV nuc...Continue Reading

References

Apr 19, 1990·The New England Journal of Medicine·M C DalakasJ L Griffin
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Jun 1, 1990·Antimicrobial Agents and Chemotherapy·S G CarterC D Rankin
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Citations

Apr 10, 2010·Cardiovascular Toxicology·James J KohlerWilliam Lewis
Jul 29, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·J T LonerganW C Mathews
Jan 6, 2001·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·G Moyle
Apr 25, 2001·The Journal of Biological Chemistry·S E Lim, W C Copeland
Aug 30, 2001·The Journal of Biological Chemistry·A A JohnsonK A Johnson

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