Ascorbic acid and trolox cell pretreatment decreases carcinogenic Cr(VI)-induced toxicity: A comparative study

Borut Poljšak, Miklós Pesti, Zoltán Gazdag, József Belagyi, Peter Raspor

Research output: Contribution to journalArticle

Abstract

The biological effects associated with Cr exposure are diverse and depend upon metal speciation. The ability of Cr(VI) to oxidize biomolecules with the formation of Cr(III) complexes is believed to be responsible for the mutagenicity and carcenogenicity of Cr(VI). However, neither Cr(VI) nor Cr(III) alone cause significant DNA damage, which is a necessary but not a sufficient first step en route to cancer. Reactive Cr(V) and Cr(IV) intermediates and reactive oxygen species, formed during the course of Cr(VI) reactions with inracelular reductants, may be the DNA-damaging species. The elucidation of these mechanisms and species responsible for the formation of oxidative DNA lesions upon Cr(VI) treatment is of continuing interest. Since endogenous antioxidant defense systems cannot be activated prior to Cr(VI)-induced oxidative stress, pretreatment with exogenous antioxidants such as ascorbic acid (vitamin C) and Trolox (a water soluble analogue of vitamin E) against Cr(VI)-induced damage was investigated using yeast Saccharomyces cerevisiae as a model organism. The antioxidative potential of ascorbic acid and Trolox was compared under the same experimental conditions in vivo. The objective of this study was to pretreat yeast cells with the same concentration of ascorbic acid and Trolox in order to increase cell tolerance against reactive chromium intermediates and reactive oxygen species formed during chromium(VI) reduction and compare ascorbic acid and Trolox antioxidative protection. Results indicate the important role of increased cytosol reduction capacity on the modification of Cr(V) formation, increased chromium accumulation, and increased scavenging ability of superoxide anions and hydrogen peroxide. Ascorbic acid and Trolox affects Cr(VI) by decreasing Cr(V) persistence, decreasing the levels of intracellular superoxide anions and peroxide formation, and quenching free radicals formed during Cr(VI) to Cr(III) reduction. Many similarities were observed between acorbic acid and Trolox antioxidative protection against Cr(VI)-induced toxicity. Use of yeast S. cerevisiae as a model organism can improve our understanding of the mechanisms by which higher eukaryotes cope with Cr(VI) toxicity.

Original languageEnglish
Pages (from-to)387-402
Number of pages16
JournalInternational Journal of Cancer Prevention
Volume2
Issue number6
Publication statusPublished - Jun 10 2009

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Keywords

  • Ascorbic acid
  • Cr(VI)
  • Reactive oxygen species
  • Trolox
  • Yeast

ASJC Scopus subject areas

  • Social Psychology
  • Oncology

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