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A Strategy to Identify Compounds that Affect Cell Growth and Survival in Cultured Mammalian Cells at Low-to-Moderate Throughput
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Cell cultures: A tool for the study of mechanisms of toxicity

C L Galli1, B Viviani, M Marinovich

  • 1Laboratory of Toxicology, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|August 25, 2010
PubMed

Insights

Tributyltin chloride (TBT) and triphenyltin chloride (TPT) disrupt cellular functions by affecting cytoskeletal components, particularly F-actin. This disruption impairs cellular responses and may serve as a marker for toxic chemical exposure.

Area of Science:

  • Toxicology
  • Cell Biology
  • Biochemistry

Background:

  • Toxic agents can impact cellular function by targeting cytoskeletal components, potentially initiating metabolic alterations.
  • Organotin compounds like TBT and TPT are known environmental contaminants with potential cellular toxicity.

Purpose of the Study:

  • To investigate the toxic effects of tributyltin chloride (TBT) on cellular functions, including ATP levels, protein synthesis, glutathione (GSH) levels, and lactate dehydrogenase (LDH) activity.
  • To examine the impact of TBT and triphenyltin chloride (TPT) on F-actin levels and cellular responses in human neutrophils.
  • To explore the potential of actin polymerization response as a biomarker for human exposure to organotin compounds.

Main Methods:

  • Investigated the effects of TBT on ATP, protein synthesis, GSH, and LDH in a murine epidermal cell line (HEL-30).
  • Assessed F-actin levels and the response to chemotactic stimulus (fMLP) in human neutrophils treated with TBT and TPT.
  • Utilized S-9 preparation and dithiothreitol (DTT) to observe recovery of cellular functions.

Main Results:

  • TBT exposure decreased ATP levels, protein synthesis, GSH levels, and altered LDH activity in HEL-30 cells.
  • Recovery of cellular functions was observed with S-9 preparation or DTT treatment.
  • TBT and TPT reduced F-actin levels in resting human neutrophils and abolished their response to fMLP.
  • SnCl(2) did not affect F-actin levels, indicating specificity of organotin compounds.

Conclusions:

  • Organotin compounds like TBT and TPT exert toxicity by interfering with cytoskeletal integrity, specifically F-actin.
  • The disruption of actin polymerization in neutrophils by TBT and TPT suggests a potential mechanism for their toxic effects.
  • The impaired actin polymerization response in neutrophils could serve as a valuable biomarker for human exposure to specific toxic chemicals like TPT.

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