Genotoxicity of organoselenium compounds in human leukocytes in vitro

D. B. Santos, V. P.P. Schiar, M. C.P. Ribeiro, R. S. Schwab, D. F. Meinerz, J. Allebrandt, J. B.T. Rocha, C. W. Nogueira, M. Aschner, N. B.V. Barbosa

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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 μM or vehicle (DMSO) for 3 h at 37 °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 10-100 μM, 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.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume676
Issue number1
DOIs
StatePublished - May 31 2009

Keywords

  • Cell viability
  • DNA damage
  • Genotoxicity
  • Leukocytes
  • Organoselenium compounds
  • Selenium

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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