Genotoxicity of acrylamide and glycidamide in human lymphoblastoid TK6 cells.
The recent finding that acrylamide (AA), a potent carcinogen, is formed in foods during cooking raises human health concerns. In the present study, we investigated the genotoxicity of AA and its metabolite glycidamide (GA) in human lymphoblastoid TK6 cells examining three endpoints: DNA damage (comet assay), clastogenesis (micronucleus test) and gene mutation (thymidine kinase (TK) assay). In a 4 h treatment without metabolic activation, AA was mildly genotoxic in the micronucleus and TK assays at high concentrations (> 10 mM), whereas GA was significantly and concentration-dependently genotoxic at all endpoints at > or = 0.5 mM. Molecular analysis of the TK mutants revealed that AA predominantly induced loss of heterozygosity (LOH) mutation like spontaneous one while GA-induced primarily point mutations. These results indicate that the genotoxic characteristics of AA and GA were distinctly different: AA was clastogenic and GA was mutagenic. The cytotoxicity and genotoxicity of AA were not enhanced by metabolic activation (rat liver S9), implying that the rat liver S9 did not activate AA. We discuss the in vitro and in vivo genotoxicity of AA and GA.
Koyama
Naoki
N
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Sakamoto
Hiroko
H
Sakuraba
Mayumi
M
Koizumi
Tomoko
T
Takashima
Yoshio
Y
Hayashi
Makoto
M
Matsufuji
Hiroshi
H
Yamagata
Kazuo
K
Masuda
Shuichi
S
Kinae
Naohide
N
Honma
Masamitsu
M
D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects; D019656:Loss of Heterozygosity / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D015162:Micronucleus Tests; D009154:Mutation; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics
D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; D013937:Thymidine Kinase