title: Effects of excess thymidylate on thymidylate low-requiring strains of Saccharomyces cerevisiae: high mutagenicity and absence of DNA strand breaks.
abstract: 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.
authors.affiliation: Institut für Mikrobiologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Federal Republic of Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bender
authors.forename: M
authors.initials: M
authors.lastname: Brendel
mesh_terms: 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*
chemical_list: D004271:DNA, Fungal; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate; D002172:Canavanine