Effects of excess thymidylate on thymidylate low-requiring strains of Saccharomyces cerevisiae: high mutagenicity and absence of DNA strand breaks.
dTMP exposure concentrations of 0.1 mM or higher are genotoxic in exponentially growing cells of thymidylate low-requiring mutants of Saccharomyces cerevisiae. Mutagenicity of excess dTMP is highest in an exposure concentration 10-fold of that needed for external supplementation of endogenously blocked thymidylate synthesis. Still higher dTMP concentrations are primarily cytotoxic. The canavanine forward-mutation system shows excess dTMP to be as potent a mutagen as irradiation by ultraviolet light. Mutagenicity of excess dTMP, however, differs from that of direct DNA-attacking mutagens in that it is highest in the absence of significant toxicity. Alkaline sucrose gradient centrifugation shows that excess dTMP does not induce significant numbers of DNA single- or double-strand breaks, while conditions of thymidylate deprivation lead to DNA-strand breaks and thymineless death.
Bender
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Institut für Mikrobiologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Federal Republic of Germany.
Brendel
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M
D002172:Canavanine / Q000494:pharmacology; D004271:DNA, Fungal / Q000187:drug effects* / Q000235:genetics; D004352:Drug Resistance, Microbial; D005838:Genotype; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013938:Thymidine Monophosphate / Q000378:metabolism* / Q000494:pharmacology; D013942:Thymine Nucleotides / Q000378:metabolism*
D004271:DNA, Fungal; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate; D002172:Canavanine