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Bioenergetics and DNA alteration of normal human fibroblasts by hexavalent chromium

W Liu1, F Chaspoul, C Botta

  • 1Biogénotoxicologie et Mutagénèse Environnementale (EA 1784-FR 3098 ECCOREV), Faculté de Pharmacie, Aix Marseille Université, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France.

Environmental Toxicology and Pharmacology
|July 27, 2011
PubMed

Insights

Hexavalent chromium (Cr(VI)) impairs human fibroblast mitochondrial function and glucose metabolism at high concentrations. Low Cr(VI) levels induce significant oxidative DNA damage, revealing distinct toxicity thresholds.

Area of Science:

  • Cell Biology
  • Toxicology
  • Mitochondrial Research

Background:

  • Hexavalent chromium (Cr(VI)) is a known environmental toxicant.
  • Its impact on cellular bioenergetics and DNA integrity requires further elucidation.
  • Mitochondrial dysfunction is a key factor in heavy metal toxicity.

Purpose of the Study:

  • To investigate the effects of Cr(VI) on mitochondrial function in normal human fibroblasts.
  • To assess the genotoxic potential of Cr(VI) by analyzing DNA damage.
  • To quantify reactive oxygen species (ROS) production.

Main Methods:

  • Measurement of cellular oxygen consumption.
  • Analysis of chromium-DNA adducts and oxidative DNA lesions using the Comet assay.
  • Quantification of ROS production.
  • Enzyme-specific DNA repair analysis (formamidopyrimidine-DNA glycosylase - Fpg).

Main Results:

  • Cr(VI) reduced oxygen consumption in a concentration-dependent manner (IC(50)=66±8μM), indicating mitochondrial dysfunction.
  • Defective glucose catabolism was observed, linked to altered mitochondrial functions.
  • Oxidative DNA base damage was induced by low Cr(VI) concentrations (0.5-3μM).
  • Significant bioenergetic disturbances occurred only at higher Cr(VI) concentrations (20-500μM).

Conclusions:

  • Cr(VI) exhibits a dual toxicity profile, inducing DNA damage at low concentrations and mitochondrial dysfunction at higher levels.
  • Mitochondrial impairment by Cr(VI) affects cellular energy metabolism.
  • These findings highlight the complex mechanisms of Cr(VI) toxicity in human cells.

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