Vanha artikkeli molekyylifarmakologian alalta :
Mol Pharmacol. 1985 Aug;28(2):200-6.
Specificity of inhibitors of poly(ADP-ribose) synthesis. Effects on nucleotide metabolism in cultured cells.
Abstract
The effects of inhibitors of poly(ADP-ribose)
synthesis on cell growth and several parameters of nucleotide
metabolism have been determined. At concentrations which produced
similar inhibitions of poly(ADP-ribose)
synthesis, 3-acetylaminobenzamide (1 mM) had no effect on L1210 cell
growth, 3-aminobenzamide (5mM) was slightly inhibitory and
3-methoxybenzamide (5 mM) was a potent inhibitor of growth. During a 2-h
incubation, none of the inhibitors affected ribo- or
deoxyribonucleotide concentrations in cells treated with or without
N-methyl-N-nitrosourea; however, N-methyl-N-nitrosourea treatment
reduced dCTP concentrations by 50%. During a 24-hr incubation,
3-aminobenzamide and 3-acetylaminobenzamide did not lower ribonucleotide
concentrations in cells grown with either undialyzed or dialyzed serum.
In contrast, 3-methoxybenzamide caused a depletion of UTP in cells
grown with undialyzed serum and caused a depletion of all purine and
pyrimidine ribonucleotides in cells grown with dialyzed serum.
3-Aminobenzamide and 3-acetylaminobenzamide had no effect on the
conversion of hypoxanthine to ATP and GTP but did slightly inhibit
incorporation of formate into ATP and GTP. 3-Methoxybenzamide inhibited
incorporation of both hypoxanthine and formate into purine
ribonucleotides. 3-Aminobenzamide, 3-acetylaminobenzamide, and
3-methoxybenzamide all inhibited glycine incorporation into ATP and GTP
and reduced both the incorporation of thymidine into DNA and the
apparent specific activity of the dTTP pool. We conclude that inhibition
of poly(ADP-ribose)
synthesis causes little or no growth inhibition and has no effect on
purine or pyrimidine nucleotide synthesis de novo. The effect of all the
inhibitors on glycine and formate metabolism may be related to an
inhibition of ADP-ribose
synthesis or may be a secondary effect of the inhibitors. The growth
inhibition and the reduction in nucleotide concentration caused by
3-methoxybenzamide are apparently secondary effects of this drug and may
result from an inhibition of phosphoribosyl pyrophosphate (PRPP) synthesis.
- PMID:
- 2991739
- [Indexed for MEDLINE]
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