Related Experiment Videos
Tributyltin stimulates apoptosis in rat thymocytes
1Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Archives of Biochemistry and Biophysics
|November 15, 1990
Summary
Tributyltin exposure in rat thymocytes rapidly increases intracellular calcium, leading to DNA fragmentation and cell death. This process, indicative of apoptosis, was blocked by calcium chelators, highlighting tributyltin's selective immunotoxicity.
Area of Science:
- Immunotoxicology
- Cellular Biology
- Environmental Health
Background:
- Organotin compounds are environmental contaminants with known toxicity.
- Tributyltin (TBT) is a widely used organotin compound with documented adverse effects on the immune system.
- The specific mechanisms underlying TBT-induced immunotoxicity, particularly in thymocytes, require further elucidation.
Purpose of the Study:
- To investigate the role of intracellular calcium (Ca2+) in tributyltin-induced thymocyte apoptosis.
- To determine the effects of other organotin compounds on thymocyte viability and Ca2+ homeostasis.
- To provide a cellular basis for the selective immunotoxicity of tributyltin.
Main Methods:
- Primary rat thymocytes were treated with varying concentrations of tributyltin and other organotin compounds.
- Cytosolic free Ca2+ levels were measured using Ca2+-sensitive dyes.
- DNA fragmentation was assessed using gel electrophoresis.
- Cell viability was determined using standard assays.
- Effects of Ca2+ chelators and extracellular Ca2+ removal were evaluated.
Main Results:
- Micromolar tributyltin induced a rapid, Ni2+-sensitive increase in cytosolic Ca2+ in thymocytes.
- This Ca2+ elevation was associated with DNA fragmentation, characteristic of apoptosis.
- Intracellular Ca2+ chelators and removal of extracellular Ca2+ prevented DNA fragmentation and loss of cell viability.
- Other organotin compounds (trimethyltin, triphenyltin, dibutyltin) showed minimal effects.
- Thymocytes exhibited a greater susceptibility to tributyltin compared to other organotins.
Conclusions:
- Tributyltin induces thymocyte apoptosis through a mechanism involving increased intracellular Ca2+ concentration.
- The observed DNA fragmentation is mediated by a Ca2+- and Mg2+-dependent endonuclease.
- Thymocytes are particularly sensitive to tributyltin, which may explain its selective immunotoxicity in vivo.
- These findings contribute to understanding the molecular mechanisms of organotin-induced immunotoxicity.