Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae--an interlaboratory assessment of 12 chemicals

Induced mitotic chromosome loss was assayed using diploid yeast strain S. cerevisiae D61.M. The test relies upon the uncovering and expression of multiple recessive markers reflecting the presumptive loss of the chromosome VII homologue carrying the corresponding wild-type alleles. An interlaboratory study was performed in which 12 chemicals were tested under code in 2 laboratories. The results generated by the Berkeley and the Darmstadt laboratories were in close agreement. The solvents benzonitrile and methyl ethyl ketone induced significantly elevated chromosome loss levels. However, a treatment regime that included overnight storage at 0 degree C was required to optimize chromosome loss induction. Hence, these agents are postulated to induce chromosome loss via perturbation of microtubular assembly. Fumaronitrile yielded inconsistent results: induction of chromosome loss and respiratory deficiency was observed in both laboratories, but the response was much more pronounced in the Darmstadt trial than that observed in Berkeley. The mammalian carcinogens, benzene, acrylonitrile, trichloroethylene, 1,1,1-trichloroethane and 1,1,1,2-tetrachloroethane failed to induce chromosome loss but elicited high levels of respiratory deficiency, reflecting anti-mitochondrial activity. Trifluralin, cyclophosphamide monohydrate, diazepam and diethylstilbestrol dipropionate failed to induce any detectable genetic effects. These data suggest that the D61.M system is a reproducible method for detecting induced chromosome loss in yeast.