PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3904715

Mutagen testing with yeast.

F Eckardt·W Siede
View original source ↗Export metadata ↓

Abstract

This article deals primarily with the practical aspects of mutagen testing with yeast. Equipment necessary for a laboratory where mutagen testing with yeast is performed, and the most commonly used media, are listed. Some general procedures are described and, finally, for those who have little experience with work of this kind, a precise protocol is given for an experiment with stationary phase cells of the strain D7 of Saccharomyces cerevisiae using the heteroallelic ade2 system as the genetic endpoint. Some experimental data were obtained by students following this protocol using the direct-acting mutagen ethyl methanesulfonate (EMS); these data are discussed and analyzed. More details on the various genetic endpoints available in numerous yeast strains and on the interpretation of dose-dependence data, as well as an extended list of yeast literature, can be found in an article by Eckardt and von Borstel in this volume. Further technical advice is provided in our references to Zimmermann (1975), von Borstel (1981), and Zimmermann et al. (1984).

Explore related subjects

Mutagenicity TestsSaccharomyces cerevisiaeJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

F Eckardt, W Siede. 1985. Mutagen testing with yeast.. https://doi.org/10.1007/978-1-4684-4976-1_19

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

A multiple in silico program approach for the prediction of mutagenicity from chemical structure.

We have conducted an evaluation of three of the most widely used commercial toxicity prediction programs, Toxicity Prediction by Komputer Assisted Technology (TOPKAT), Deductive Estimation of Risk from Existing Knowledge (DEREK) for Windows (DfW) and CASETOX. The three programs were evaluated for their ability to predict Ames test mutagenicity using 520 proprietary drug candidate (Test set 1) and 94 commercial (Test set 2) compounds. The study demonstrates that these three commercially available programs are useful, with limitations in their ability to predict mutagenicity over a wide range of chemical space, i.e. global predictivity. Individually, each of the programs performed at an acceptable level for overall accuracy, i.e. the ability to predict the correct outcome. However, analysis of the predictions indicates that the overall accuracy figure is heavily weighted by the ability of the programs to correctly predict non-mutagens, whereas none of the programs individually performed well in the prediction of novel mutagenic structures, i.e. Ames positive compounds. The performance of these programs' in predicting Ames positive mutagens appeared to be independent of the chemical utility of the compound, i.e. industrial, agricultural or pharmaceutical. The combination of program predictions provided some improvement in overall accuracy, sensitivity and specificity.

Mutagenicity Tests↗
PubMed2003

Structure-activity relationship of oxadiazoles and allylic structures in the Ames test: an industry screening approach.

In recent years genotoxicity testing has become more and more important in the process of early screening for potential development compounds. In the case that a pharmacologically interesting structure is found to be positive in an in vitro mutagenicity test a straightforward approach starts by sorting out what substructure is responsible for the activity observed in the test. The Ames test is a rapid, convenient test system which has been effectively used in structure-activity relationship studies for mutagenicity, since it can rapidly establish differences in the mutagenic action of isomers and chemical analogs. The lead compound with a benzodiazepine-like structure and close analogs exhibited weak, but unequivocal positive effects in the Ames test (strains TA1535 and TA 100) after metabolic activation by rat liver homogenate fraction (S9). To identify substances within this class of compounds devoid of mutagenic liability an extensive structure-activity investigation was undertaken. More than 50 compounds were tested in the two critical bacterial strains, using a standard plate incorporation and a preincubation modification. It quickly became evident that the benzodiazepine structure was not involved. First hints that the allyl side chain were responsible for the Ames activity had to be refined in a more complex, but clear-cut structure-activity relationship during the course of the experiments. It was shown that all compounds with an allyl side chain, independent of the heterocycle, but surprisingly also all compounds with a specific arrangement of the heteroatoms in the oxadiazole ring, showed positive effects in at least one strain. Based on these investigations it was possible to select pharmacologically active structures without mutagenic liability.

Mutagenicity Tests↗