Influence of different factors on the induction of chromosome malsegregation in Saccharomyces cerevisiae D61.M by bavistan and assessment of its genotoxic property in the Ames test and in Saccharomyces cerevisiae D7.
Bavistan is known to be a potent inducer of chromosome malsegregation in Saccharomyces cerevisiae. The influence of different factors on the induction of chromosome malsegregation in S. cerevisiae D61.M was investigated. With both standard protocols used (16 h overnight incubation and cold treatment protocol) bavistan, in a concentration range of 2.5-20 micrograms/ml, induced malsegregants to the same extent. The frequencies of malsegregants obtained were not influenced by the plating volume used on selective medium. Induction of malsegregants and toxicity became stronger with increasing supplementation of the incubation medium with yeast extract and peptone. The effects of bavistan on chromosome malsegregation were more pronounced at 28 degrees C--the normal temperature for yeast growth--as compared to 33 and 37 degrees C. A study of the time dependence of the induction of chromosome loss showed that malsegregants can already be detected after 8 h and 1.5 h (second incubation period) using the incubation protocols without and with cold treatment, respectively. To clarify whether a selection towards malsegregants occurs, the growth of mixed cultures of red, cycloheximide-sensitive cells and white, cycloheximide-resistant, leucine-auxotrophic cells prepared at different ratios was compared. A strong selection towards red cells and against the malsegregants was observed. In addition, bavistan was tested for genotoxic activity in Salmonella (Ames test) and in yeast S. cerevisiae D7. No mutagenic activity was detected using S. cerevisiae D7 (gene conversion, reverse mutation, mitotic crossing-over) with and without rat-liver S9. In contrast bavistan induced histidine revertants in the frameshift strains TA1537, TA1538, TA97 and TA98 of Salmonella typhimurium after addition of an exogenous metabolic activation system.
Albertini
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Department of Toxicology, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D002219:Carbamates; D002869:Chromosome Aberrations; D003513:Cycloheximide / Q000633:toxicity; D005659:Fungicides, Industrial / Q000493:pharmacokinetics / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D009153:Mutagens; D003513:Cycloheximide; C006698:carbendazim