Comparison of three forward mutation systems in Saccharomyces cerevisiae for sensitivity to polycyclic and heterocyclic compounds.
Forward mutation to cycloheximide resistance, L-canavanine resistance and DL-alpha-aminoadipic acid resistance in Saccharomyces cerevisiae wild-type strain S7a was tested for sensitivity to nine mutagens in treat-and-plate assays. Eight of these agents, 2-aminofluorene, 2-acetylaminofluorene, benzo[a]pyrene, benzidine, cyclophosphamide, acriflavine, 7,12-dimethylbenz[a]anthracene and 2-aminoanthracene were known or suspected to be difficult to detect whilst one, methyl methanesulphonate, was known to be very active in yeast. Forward mutation to cycloheximide resistance was, overall, the most sensitive system, detecting all nine agents under optimal conditions, although neither benzidine nor benzo[a]pyrene were consistently positive. Mutation to adipic acid resistance occasionally gave responses superior to those at the cycloheximide loci, but mutation to canavanine resistance was never more sensitive than the cycloheximide resistance system. We conclude that forward mutation in strain S7a using both cycloheximide and adipic acid resistance loci is capable of detecting the genetic effects of a range of polycyclic and heterocyclic compounds with greater sensitivity than is seen in other published gene mutation assays with yeast. Although sensitivity is much lower than in bacterial assays, such yeast assays provide a reasonable alternative to bacterial genotoxicity screening for agents such as potent bactericides.
Mitchell
I
I
SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn, Herts, UK.
Gilbert
P J
PJ
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D006571:Heterocyclic Compounds; D009153:Mutagens; D011083:Polycyclic Compounds; D015074:2-Aminoadipic Acid; D002172:Canavanine; D003513:Cycloheximide