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

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.

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
11.9K
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
13.8K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
2.0K
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
229