PMID: 6403046Jan 25, 1983Paper

The effect of chemical mutagens on purine and pyrimidine nucleotide biosynthesis

Biochimica Et Biophysica Acta
E VolkinM H Jones

Abstract

Nucleotide biosynthesis in Novikoff hepatoma cells is markedly altered by a variety of chemical mutagens, whether the mechanism of mutagenesis is by base substitution, covalent binding (adduct formation), intercalation, or cross-linking of DNA. The compounds investigated (N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide, 9-aminoacridine, and mitomycin C), at concentrations that cause some inhibition of RNA and DNA synthesis, bring about a large increase in the pool levels of all four nucleoside triphosphates. At the same time, reactions leading to the synthesis of CTP from exogenous uridine and GTP and ATP from exogenous hypoxanthine are severely inhibited. The formation of UTP from uridine and ATP from adenosine, by more direct phosphorylation reactions, appears relatively unaffected. The increase in nucleotide pool size cannot be accounted for by a corresponding increase in de novo purine and pyrimidine nucleotide synthesis, as experiments with labeled formate and aspartate show similar inhibitions by the mutagens. With the salvage precursors, [3H]uridine and [3H]hypoxanthine, the mutagens can produce a widely divergent reduction in the labeling of RNA-CMP versus RNA-UMP and of RNA-GMP versus RNA-AMP, mostly a r...Continue Reading

Citations

Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Jan 1, 1985·The International Journal of Biochemistry·E Kukko-Kalske, J Heinonen
Jul 1, 1988·Mutation Research·E T Snow, S Mitra
Jan 1, 1995·Environmental and Molecular Mutagenesis·A J EdwardsB J Phillips

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