title: Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood.
abstract: 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 0.5 microM, AA was inactive up to a concentration of 10 mM. In contrast, GA showed a concentration dependent induction of mutations at concentrations of 800 microM 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 6000 microM. With GA, concentration dependent DNA damage was observed in the dose range of 300-3000 microM after 4 h incubation. Significant MN-induction was not observed with AA (up to 5000 microM) and GA (up to 1000 microM), whereas BL (4 microM) induced significantly enhanced MN frequencies. Thus, in our systems GA appears to exert a rather moderate genotoxic activity.
authors.affiliation: Division of Food Chemistry and Environmental Toxicology, Department of Chemistry, University of Kaiserslautern, D-67663 Kaiserslautern, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Baum
authors.forename: Evelyne
authors.initials: E
authors.lastname: Fauth
authors.forename: Silke
authors.initials: S
authors.lastname: Fritzen
authors.forename: Armin
authors.initials: A
authors.lastname: Herrmann
authors.forename: Peter
authors.initials: P
authors.lastname: Mertes
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Merz
authors.forename: Melanie
authors.initials: M
authors.lastname: Rudolphi
authors.forename: Heinrich
authors.initials: H
authors.lastname: Zankl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Eisenbrand
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*
chemical_list: D004852:Epoxy Compounds; D009153:Mutagens; D020106:Acrylamide; C071834:glycidamide