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Antimicrob Agents Chemother. 1994 Dec;38(12):2743-9.

Effects of antiviral nucleoside analogs on human DNA polymerases and mitochondrial DNA synthesis.

Author information

1
Division of Virology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.

Abstract

Inhibition constants were determined for 16 nucleoside analog triphosphates against human DNA polymerases alpha, beta, gamma, and epsilon, and 7 nucleoside analogs were examined as inhibitors of mitochondrial DNA synthesis in human Molt-4 cells in culture. The results demonstrate no clear quantitative or qualitative correlation between inhibition of DNA polymerases, particularly mitochondrial DNA polymerase gamma, and the inhibition of mitochondrial DNA synthesis in Molt-4 cell culture. Furthermore, the data indicate that inhibition of isolated DNA polymerases may not be predictive of in vitro or in vivo toxicity. Finally, it is not clear whether inhibition of mitochondrial DNA synthesis will be an accurate predictor of the potential in vivo toxicity of antiviral nucleoside analogs.

PMID:
7695256
PMCID:
PMC188279
DOI:
10.1128/aac.38.12.2743
[Indexed for MEDLINE]
Free PMC Article

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