Genotoxicity of excess thymidylate in thymidylate low-requiring Saccharomyces cerevisiae is associated with changes in phosphate metabolism.
When dTMP in concentrations greater than 100 microM is offered to growing cells of thymidylate low-requiring yeast strains it is both mutagenic and toxic. At exposure concentrations greater than 1 mM dTMP interferes significantly with the low-affinity phosphate permease even in the presence of exogenous phosphate concentrations of 6 mM. Chemical analysis and 31P NMR spectroscopy reveal that excess dTMP disturbs phosphate metabolism in thymidylate low-requiring strains but not in the wild type. The most prominent changes in phosphorus-containing molecules are found in polyphosphates of which up to 20% are broken down within a 20-min time span with a concomitant increase in orthophosphate pools.
Holderried
J
J
Institut für Mikrobiologie der Johann Wolfgang Goethe-Universität, Frankfurt am Main, F.R.G.
Liedtke
H
H
Brendel
M
M
D001692:Biological Transport; D002470:Cell Survival; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation; D010710:Phosphates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D013938:Thymidine Monophosphate / Q000633:toxicity*; D013942:Thymine Nucleotides / Q000633:toxicity*
D010710:Phosphates; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate