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Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay
Author(s) -
Von Tungeln Linda S.,
Doerge Daniel R.,
Gamboa da Costa Gonçalo,
Matilde Marques M.,
Witt William M.,
Koturbash Igor,
Pogribny Igor P.,
Beland Frederick A.
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27493
Subject(s) - acrylamide , carcinogen , chemistry , metabolite , body weight , genotoxicity , dna adduct , bioassay , endocrinology , hepatocellular carcinoma , toxicity , medicine , biochemistry , biology , genetics , organic chemistry , copolymer , polymer
Acrylamide is a high‐volume industrial chemical, a component of cigarette smoke, and a product formed in certain foods prepared at high temperatures. Previously, we compared the extent of DNA adduct formation and mutations in B6C3F 1 / Tk mice treated neonatally with acrylamide or glycidamide to obtain information concerning the mechanism of acrylamide genotoxicity. We have now examined the tumorigenicity of acrylamide and glycidamide in mice treated neonatally. Male B6C3F 1 mice were injected intraperitoneally on postnatal days 1, 8 and 15 with 0.0, 0.14 or 0.70 mmol acrylamide or glycidamide per kg body weight per day and the tumorigenicity was assessed after 1 year. Survival in each of the groups was >87%, there were no differences in body weights among the groups, and the only treatment‐related neoplasms involved the liver. The incidence of combined hepatocellular adenoma or carcinoma was 3.8% in the control group, 8.3% in the 0.14 mmol acrylamide and glycidamide per kg body weight groups, 4.2% in the 0.70 mmol acrylamide per kg body weight group and 71.4% in the 0.70 mmol glycidamide per kg body weight group. Analysis of the hepatocellular tumors indicated that the increased incidence observed in mice administered 0.70 mmol glycidamide per kg body weight was associated with A → G and A → T mutations at codon 61 of H‐ ras . These results, combined with our previous data on DNA adduct formation and mutation induction, suggest that the carcinogenicity of acrylamide is dependent on its metabolism to glycidamide, a pathway that is deficient in neonatal mice.