Genotoxicity of organoselenium compounds in human leukocytes in vitro

Mutat Res. 2009 May 31;676(1-2):21-6. doi: 10.1016/j.mrgentox.2009.03.006. Epub 2009 Apr 2.

Abstract

DNA damage and cell viability of human leukocytes cells were examined as simple tests for screening the potential toxicity of organoselenium compounds. Leukocytes were incubated with different organoselenium compounds at 4, 10, 40 and 100 microM or vehicle (DMSO) for 3h at 37 degrees C before of in vitro assays. Cell viability was determined by Trypan blue exclusion. DNA damage was assessed using the alkaline comet assay with silver staining. The exposure of leukocytes to (S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl, (S)-2-amino-1-diselenide-3-phenylpropanyl, 3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide, in the range of 10-100muM, induced a significant increase in Damage Index (DI). The genotoxic effect of all compounds was associated with high frequencies of cells with damage level 4 and all compounds caused a decrease in cell viability. Our results suggest that the selenium compounds tested were genotoxic and cytotoxic to human leukocytes cells in vitro and that the organoselenium amino acid derivatives ((S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl and (S)-2-amino-1-diselenide-3-phenylpropanyl) were more genotoxic than aromatic derivatives (3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide). These effects may be linked to the pro-oxidant activity exhibited by selenium compounds when used in relatively high concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Benzene Derivatives / pharmacology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • DNA Damage / drug effects*
  • DNA Damage / genetics
  • Free Radical Scavengers / pharmacology
  • Humans
  • Leukocyte Count / methods
  • Leukocytes / drug effects*
  • Leukocytes / metabolism
  • Mutagenicity Tests / standards*
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / toxicity
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / pharmacology
  • Selenium Compounds / pharmacology

Substances

  • Antioxidants
  • Benzene Derivatives
  • Free Radical Scavengers
  • Organoselenium Compounds
  • Reactive Oxygen Species
  • Selenium Compounds
  • diphenyldiselenide