Two systems, one for detecting chemically induced chromosome gain in mitotic and meiotic cells and one for mitotic chromosome loss, shall be used for the routine screening of chemicals that induce chromosome loss or gain in the yeast Saccharomyces cerevisiae. During the course of this contract it is anticipated that approximately 80 chemicals shall be tested under code for mitotic and meiotic chromosome gain and for mitotic chromosome loss. During the course of the contract, a protocol shall be developed for a single 'fusion' strain. This strain will enable detection of mitotic loss and gain as well as meiotic gain. Following validation, the balance of chemicals not already tested in the individual gain and loss systems, will be tested in the fusion system so that a total of approximately 80 coded chemicals will have been tested for the three endpoints. As needed, but for no more than 20 chemicals, isolates shall be examined genetically using tetrad analysis and/or physically for chromosomal changes. Other genetic endpoints such as recombination, mutation and mitochrondrial mutations shall be monitored according to the genetic capability of the strains. The contractor will be expected to continue to refine the system and the protocol to optimize detection of chemically induced chromosome loss and gain. This will include the refinement of techniques for karyotypic analysis of loss/gain and development of possible chemical mixture systems for assessment of loss/gain induction. Some chemicals which are not aneugenic on their own, become effective inducers of aneuploidy when combined with a low dose of a known aneuploidogen. The contractor will be expected to continue to explore the mechanisms of aneuploidy, investigate the use of permeability mutants to enhance the range of chemicals detected, and investigate the isolation of mutants affecting aneuploidy induction by solvents.
