Combined cadmium and thiuram show synergistic toxicity and induce mitochondrial petite mutants
Hitoshi Iwahashi1, Emi Ishidou, Emiko Kitagawa
1Human 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
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.
Insights
This study reveals synergistic toxicity of cadmium and thiuram in yeast, primarily damaging mitochondria. Transcriptome bioassays effectively identified this enhanced toxicity, not seen with individual chemicals.
Area of Science:
- Environmental toxicology
- Molecular biology
- Biochemistry
Background:
- Bioassays monitor environmental chemical toxicity using organismal responses.
- DNA microarrays analyze genome-wide mRNA expression for toxicity detection.
- Cadmium and thiuram showed mutual growth inhibition in yeast.
Purpose of the Study:
- To evaluate synergistic toxicity of cadmium and thiuram in yeast.
- To investigate the underlying molecular mechanisms of combined toxicity.
- To demonstrate the utility of transcriptome bioassays for synergistic toxicity assessment.
Main Methods:
- Application of DNA microarrays for genome-wide mRNA expression analysis.
- Hierarchical cluster analysis of mRNA expression profiles.
- Functional gene characterization and petite colony formation assay for mitochondrial damage.
Main Results:
- Yeast response to cadmium and thiuram combination resembled cadmium treatment alone.
- Combined treatment enhanced cadmium toxicity, specifically damaging mitochondrial functions.
- Mitochondrial damage was confirmed by increased petite colony formation frequency.
Conclusions:
- Cadmium and thiuram exhibit synergistic toxicity in yeast, leading to mitochondrial dysfunction.
- Transcriptome bioassays are effective tools for identifying and evaluating synergistic toxicity.
- This approach can reveal complex toxicological interactions in environmental monitoring.
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