PMID: 6408395Jul 1, 1983Paper

Preferential inhibition of 5-trifluoromethyl-2'-deoxyuridine phosphorylation by 5'-amino-5'-deoxythymidine in uninfected versus herpes simplex virus-infected cells

Molecular Pharmacology
P H FischerR Kawahara

Abstract

The cytotoxic effects of 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd) were effectively antagonized by 5'-amino-5'-deoxythymidine (5'-AdThd). The antiproliferative actions of CF3dUrd were reduced in a dose-dependent manner by 5'-AdThd in both HeLa and Vero cells. In addition, the ability of CF3dUrd to kill HeLa cells (95% at 1 microM and 99% at 3 microM), as measured by cloning efficiency, was ablated entirely by 5'-AdThd (300 microM). In contrast, the inhibition of herpes simplex virus Type 2 (HSV-2) replication in HeLa cells was not antagonized by 5'-AdThd. In Vero cells, the combination of CF3dUrd and 5'-AdThd produced a greater antiviral effect than either agent alone. The reduction in CF3dUrd cytotoxicity caused by 5'-AdThd in uninfected HeLa and Vero cells was associated with decreased intracellular levels of CF3dUrd nucleotides. In contrast, in HSV-2-infected Vero cells the intracellular levels of CF3dUrd nucleotides were slightly elevated by 5'-AdThd and, in virally infected HeLa cells, a 300-fold excess of 5'-AdThd reduced CF3dUrd uptake only marginally. Since the relative abundance of these phosphorylated derivatives of CF3dUrd was not markedly changed by 5'-AdThd, preferential inhibition of the mammalian thymidine kina...Continue Reading

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