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Genotoxicity of glycidamide in comparison to (±)‐anti‐benzo[ a ]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide and α‐acetoxy‐ N ‐nitroso‐diethanolamine in human blood and in mammalian V79‐cells
Author(s) -
Thielen Silke,
Baum Matthias,
Hoffmann Michelle,
Loeppky Richard N.,
Eisenbrand Gerhard
Publication year - 2006
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200500227
Subject(s) - genotoxicity , benzo(a)pyrene , chemistry , epoxide , diethanolamine , stereochemistry , toxicology , carcinogen , biochemistry , organic chemistry , biology , toxicity , catalysis
Genotoxic activity of glycidamide (GA) was investigated in comparison to that of the known carcinogens (±)‐anti‐benzo[ a ]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide ((±)‐BPDE) and α‐acetoxy‐ N ‐nitroso‐diethanolamine (α‐A‐NDELA), using the hypoxanthine‐phosphoribosyl‐transferase ( hPRT ) gene mutation assay with V79 mammalian cells and modified alkaline single cell gel electrophoresis (alkaline comet assay with and without treatment of cells with formamido‐pyrimidine‐DNA‐glycosylase (FPG)) in lymphocytes from human whole blood. As shown earlier, GA induced significant DNA damage in lymphocytes from treated whole blood at ⪈300 μM (4 h) (Baum et al. , Mutat. Res. 2005, 580 , 61–69). In the present study, using the alkaline comet assay with FPG treatment, increased formation of DNA strand breaks was observed in lymphocytes treated with GA (10 μM; 4 h). α‐A‐NDELA and (±)‐BPDE were genotoxic at 10–30 μM (1 h). Genotoxic activity of these compounds was not enhanced after FPG treatment. FPG treatment thus offers an enhanced sensitivity of DNA damage detection for genotoxic compounds with preference for N 7 ‐ resp. N 3 ‐purine alkylation. In the hPRT assay with V79 cells, mutagenic activity of (±)‐BPDE became significant at ⪈3 μM (24 h). For α‐A‐NDELA significant activity was observed at ⪈10 μM (24 h). As previously observed, GA was considerably less effective, inducing significant mutagenicity roughly at about 80–300‐fold higher concentrations (800 μM; 24 h) (Baum et al. , Mutat. Res. 2005, 580 , 61–69).