Comparison of the genetic activity of dimethylnitrosamine, ethyl methanesulfonate, 2-acetylaminofluorene and ICR-170 in Saccharomyces cerevisiae strains D3, D4 and D5 using in vitro assays with and without metabolic activation

Abstract

Summary Three strains of Saccharomyces cerevisiae D3, D4 and D5, routinely employed in assays to evaluate the genetic properties of chemicals were compared for their ability to respond to four known mutagens. The comparisons were conducted using in vitro assays with and without the incorporation of hepatic metabolic enzyme fractions from mice. Two of the mutagens, ethyl methanesulfonate (EMS) and 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl) aminopropyl-aminolacridine dihydrochloride (ICR-170) are directly active in vitro and were shown to induce mitotic events in all three strains. At a 1.0% concentration, EMS exhibited greatest activity against strain D3 followed by D5 and D4 respectively. ICR-170 at a dose of 10 μg/ml demonstrated similar levels of activity in strains D3 and D5 with only slightly lower activity in strain D4. The remaining two compounds dimethylnitrosamine (DMNA) and 2-acetylaminofluorene (AAF) require metabolic activation to genetically active intermediates which necessitated the addition of an enzyme system to the assay. DMNA at 77.0 ηmoles/ml was most active against strain D4 with strains D3 and D5 responding approximately equal to each other. AAF did not demonstrate any genetic activity in any of the strains. Sensitivity and utility of the three yeast strains are discussed.