title: Combined cadmium and thiuram show synergistic toxicity and induce mitochondrial petite mutants.
abstract: A bioassay is a system for monitoring toxicity of chemicals in the environment via the biological responses of experimental organisms. These responses can be detected by analysis of genome-wide changes in mRNA expression levels using DNA microarrays. We applied this system for evaluation of synergistic toxicity by cadmium and thiuram, as this combination showed mutual growth inhibition in yeast. Hierarchical cluster analysis using mRNA expression profiles suggested the response of yeast to this combination is similar to that seen with cadmium treatment alone. Functional characterization of genes induced by this combinational treatment also suggests that the toxicity of cadmium was enhanced. This toxicity was observed as the damage to mitochondrial functions, which were not observed with either cadmium or thiuram treatments alone. The potential toxicity to mitochondria by this combinational treatment was confirmed as the result of deletion of mitochondria with petite colony formation frequency. We could evaluate synergistic toxicity by cadmium and thiuram and show the possible use of transcriptome bioassay for synergistic toxicity.
authors: Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Onogawa 16-1, Tsukuba, Ibaraki 305-8569, Japan. hitoshi.iwahashi@aist.go.jp
authors: Hitoshi
authors: H
authors: Iwahashi
authors: Emi
authors: E
authors: Ishidou
authors: Emiko
authors: E
authors: Kitagawa
authors: Yuko
authors: Y
authors: Momose
mesh_terms: D001681:Biological Assay; D002104:Cadmium / Q000032:analysis* / Q000737:chemistry; D016000:Cluster Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013893:Thiram / Q000032:analysis*
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D002104:Cadmium; D013893:Thiram