Genotoxicity of organoselenium compounds in human leukocytes in vitro.
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.
Santos
D B
DB
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Brazil.
Schiar
V P P
VP
Ribeiro
M C P
MC
Schwab
R S
RS
Meinerz
D F
DF
Allebrandt
J
J
Rocha
J B T
JB
Nogueira
C W
CW
Aschner
M
M
Barbosa
N B V
NB
D000975:Antioxidants / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007958:Leukocyte Count / Q000379:methods; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests / Q000592:standards*; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology; D018036:Selenium Compounds / Q000494:pharmacology
D000975:Antioxidants; D001555:Benzene Derivatives; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; C061132:diphenyldiselenide