Genotoxicity of glycidamide in comparison to (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide and alpha-acetoxy-N-nitroso-diethanolamine in human blood and in mammalian V79-cells.
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 alpha-acetoxy-N-nitroso-diethanolamine (alpha-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 > or = 300 microM (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 microM; 4 h). alpha-A-NDELA and (+/-)-BPDE were genotoxic at 10-30 microM (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 > or = 3 microM (24 h). For alpha-A-NDELA significant activity was observed at greater, not dbl 10 microM (24 h). As previously observed, GA was considerably less effective, inducing significant mutagenicity roughly at about 80-300-fold higher concentrations (800 microM; 24 h) (Baum et al., Mutat. Res. 2005, 580, 61-69).
Thielen
Silke
S
Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Germany.
Baum
Matthias
M
Hoffmann
Michelle
M
Loeppky
Richard N
RN
Eisenbrand
Gerhard
G
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000097:blood; D004249:DNA Damage / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D004852:Epoxy Compounds / Q000633:toxicity*; D005347:Fibroblasts; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008168:Lung; D008214:Lymphocytes / Q000737:chemistry; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation
D004852:Epoxy Compounds; D009153:Mutagens; C510965:alpha-acetoxy-N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C071834:glycidamide; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase