title: The global effect of exposing bakers' yeast to 5-fluoruracil and nystatin; a view to Toxichip.
abstract: A genome-wide screen of a haploid deletion library of bakers' yeast (Saccharomyces cerevisiae) was conducted to document the phenotypic and transcriptional impact of exposure to each of the two pharmaceutical products 5-fluorouracil (an anti-tumor agent) and nystatin (an anti-fungal agent). The combined data set was handled by applying a systems biology perspective. A Gene Ontology analysis identified functional categories previously characterized as likely targets for both compounds. Induced transcription profiles were well correlated in yeast and human HepG2 cells. The identified molecular targets for both compounds were used to suggest a small set of human orthologues as appropriate for testing on human material. The yeast system developed here (denoted "Toxichip") has likely utility for identifying biomarkers relevant for health and environmental risk assessment applications required as part of the development process for novel pharmaceuticals.
authors.affiliation: Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Graziano
authors.affiliation: Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
authors.forename: Mariolina
authors.initials: M
authors.lastname: Gullì
authors.affiliation: Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Maestri
authors.affiliation: Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy. Electronic address: nelson.marmiroli@unipr.it.
authors.forename: Nelson
authors.initials: N
authors.lastname: Marmiroli
mesh_terms: D000935:Antifungal Agents / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers; D005472:Fluorouracil / Q000633:toxicity*; D006801:Humans; D009761:Nystatin / Q000633:toxicity*; D018570:Risk Assessment; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology; D018675:Toxicity Tests / Q000379:methods*; D014158:Transcription, Genetic
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D015415:Biomarkers; D009761:Nystatin; D005472:Fluorouracil
keywords: Functional toxicogenomics; Genome-wide screening; Saccharomyces cerevisiae; Toxichip