Mechanism of the lethal and mutagenic effects of phenoxyacetic acids in Saccharomyces cerevisiae.
MCPA and salicylic acid, two compounds with similar structures and almost the same dissociation pattern, were tested for lethal and mutagenic effects on, and uptake by, cells of Saccharomyces cerevisiae strain rad18. The results obtained with the two compounds were similar, suggesting a common mechanism of action. It is proposed that they act by increasing the concentration of hydrogen ions within the cell, so that killing and mutation occur. Mutations were induced only when killing reached 95--99%. The compounds are considered weak mutagens for yeast cells. The methyl ester of MCPA also induced killing and reverse mutation, but only at concentrations about 100 times higher than for the undissociated acid. MCPA methyl ester did not increase the number of revertants in the Salmonella/liver microsome test. It is suggested that the effects of the methyl ester of MCPA depends on the ester being hydrolysed to the acid by yeast cells and the liver microsome preparation.
D004353:Drug Evaluation, Preclinical; D005821:Genetic Techniques; D006016:Glycolates / Q000494:pharmacology*; D009153:Mutagens; D010642:Phenoxyacetates / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics
D006016:Glycolates; D009153:Mutagens; D010642:Phenoxyacetates