Genotoxicity of acrylamide in vitro: Acrylamide is not metabolically activated in standard in vitro systems.
The recent finding that acrylamide (AA), a genotoxic rodent carcinogen, is formed during the frying or baking of a variety of foods raises human health concerns. AA is known to be metabolized by cytochrome P450 2E1 (CYP2E1) to glycidamide (GA), which is responsible for AA's in vivo genotoxicity and probable carcinogenicity. In in-vitro mammalian cell tests, however, AA genotoxicity is not enhanced by rat liver S9 or a human liver microsomal fraction. In an attempt to demonstrate the in vitro expression of AA genotoxicity, we employed Salmonella strains and human cell lines that overexpress human CYP2E1. In the umu test, however, AA was not genotoxic in the CYP2E1-expressing Salmonella strain or its parental strain. Moreover, a transgenic human lymphoblastoid cell line overexpressing CYP2E1 (h2E1v2) and its parental cell line (AHH-1) both showed equally weak cytotoxic and genotoxic responses to high (>1 mM) AA concentrations. The DNA adduct N7-GA-Gua, which is detected in liver following AA treatment in vivo, was not substantially formed in the in vitro system. These results indicate that AA was not metabolically activated to GA in vitro. Thus, AA is not relevantly genotoxic in vitro, although its in vivo genotoxicity was clearly demonstrated.
Koyama
Naoki
N
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan.
Yasui
Manabu
M
Oda
Yoshimitsu
Y
Suzuki
Satoshi
S
Satoh
Tetsuo
T
Suzuki
Takuya
T
Matsuda
Tomonari
T
Masuda
Shuichi
S
Kinae
Naohide
N
Honma
Masamitsu
M
D020106:Acrylamide / Q000378:metabolism* / Q000633:toxicity*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004852:Epoxy Compounds / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D012475:Salmonella / Q000187:drug effects / Q000235:genetics
D018736:DNA Adducts; D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; D019392:Cytochrome P-450 CYP2E1