Lack of mitochondrial toxicity in CEM cells treated with carbovir

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 pr...

Full description

Saved in:

Bibliographic Details
Published in:	Antiviral research Vol. 34; no. 3; pp. 131 - 136
Main Authors:	Parker, William B, Shaddix, S.C, Vince, Robert, Bennett, L.Lee
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-05-1997 Elsevier
Subjects:	1592U89 Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - virology Anti-HIV Agents - toxicity Biological and medical sciences Carbovir Cell Line Delayed cytotoxicity Dideoxynucleosides - toxicity DNA, Mitochondrial - biosynthesis Drug Evaluation, Preclinical Drug toxicity and drugs side effects treatment human immunodeficiency virus Humans Lactic acid Lactic Acid - metabolism Medical sciences Miscellaneous (drug allergy, mutagens, teratogens...) Mitochondria - drug effects Mitochondria - metabolism Mitochondrial DNA synthesis Pharmacology. Drug treatments Prodrugs - toxicity Zalcitabine - toxicity Mitochondrial DNA synthesis CBV-TP, 5′-triphosphate of CBV CBV, carbovir 1592U89 CBV-MP, 5′-monophosphate of CBV IC 50, concentration of drug required to inhibit cell growth by 50 D4T, 2′,3′-dideoxy-2′,3′-didehydrothymidine ddCTP, 5′-triphosphate of ddC 3TC, 2′,3′-dideoxy-3′-thiacytidine 3TC-TP, 5′-triphosphate of 3TC Carbovir ddC, 2′,3′-dideoxycytidine AZT, 3′-deoxy-3′-azidothymidine ddI, 2′,3′-dideoxyinosine Lactic acid Delayed cytotoxicity Immunopathology Cell culture Purine nucleoside Toxicity Retroviridae AIDS Mitochondrial DNA Immune deficiency In vitro Guanine Infection Virus Mitochondria Synthesis Viral disease Delayed toxicity Lentivirinae Antiviral Human immunodeficiency virus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 μM 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 μM 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 nucleoside analogs.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0166-3542 1872-9096
DOI:	10.1016/S0166-3542(97)01033-4