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Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood

Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood,10.1016/j.mrgentox.2004.11.007,Mutation Research-genetic Toxicology and Env

Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood   (Citations: 17)
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Acrylamide (AA) can be formed in certain foods by heating, predominantly from the precursor asparagine. It is a carcinogen in animal experiments, but the relevance of dietary exposure for humans is still under debate. There is substantial evidence that glycidamide (GA), metabolically formed from AA by Cyp 2E1-mediated epoxidation, acts as ultimate mutagenic agent. We compared the mutagenic potential of AA and GA in V79-cells, using the hprt mutagenicity-test with N-methyl-N′-nitro-N-nitroso-guanidine (MNNG) as positive control. Whereas MNNG showed marked mutagenic effectivity already at 0.5μM, AA was inactive up to a concentration of 10mM. In contrast, GA showed a concentration dependent induction of mutations at concentrations of 800μM and higher. Human blood was used as model system to investigate genotoxic potential in lymphocytes by single cell gel electrophoresis (comet assay) and by measuring the induction of micronuclei (MN) with bleomycin (BL) as positive control. AA did not induce significant genotoxicity or mutagenicity up to 6000μM. With GA, concentration dependent DNA damage was observed in the dose range of 300–3000μM after 4h incubation. Significant MN-induction was not observed with AA (up to 5000μM) and GA (up to 1000μM), whereas BL (4μM) induced significantly enhanced MN frequencies. Thus, in our systems GA appears to exert a rather moderate genotoxic activity.
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    • ...Our results are in agreement with Baum et al. (2005), who also did not find AA genotoxicity in the comet assay with human blood cells at 1–4 h of incubation...

    Marta Pingarilhoet al. Genetic Polymorphisms in Detoxification and DNA Repair Genes and Susce...

    • ...This metabolic conversion appears to be critical for the genotoxicity of AA because when the mutagenicity of AA and that of GA have been compared, GA has typically been more potent (Baum et al., 2005; Besaratinia and Pfeifer, 2004; Koyama et al. ,2 006; Manjanatha et al., 2006)...
    • ...Additionally, at concentrations up to 4mM for AA and up to 1mM for GA, the cell survival was clearly above 50%, indicating that the cytotoxicity of both compounds would not hinder the cytogenetic studies (Fig. 2). These results are in agreement with data recently reported by other groups, using different cell survival end points (Baum et al., 2005; Koyama et al., 2006)...

    Celia Martinset al. Cytogenetic Damage Induced by Acrylamide and Glycidamide in Mammalian ...

    • ...More recent studies with the metabolite GLY show alterations in the HGPRT locus in V-79 cells and other genetic damage in human blood cells in vitro (Baum et al, 2005), in addition to formation of adducts with adenine and guanine bases in a variety of tissues following in vivo exposure (Doerge et al, 2005a; Maniere et al, 2005)...

    J. H. Exon. A Review of the Toxicology of Acrylamide

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