Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay.

Abstract

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.

• Authors: Linda S Von Tungeln, Daniel R Doerge, Gonçalo Gamboa da Costa, M Matilde Marques, William M Witt, Igor Koturbash, Igor P Pogribny, Frederick A Beland
• Journal: International journal of cancer (Int J Cancer) Vol. 131 Issue 9 Pg. 2008-15 (Nov 01 2012) ISSN: 1097-0215 [Electronic] United States
• PMID: 22336951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2012 UICC.

Chemical References

• Carcinogens
• DNA Adducts
• Epoxy Compounds
• Acrylamide
• glycidamide

Topics

• Acrylamide (metabolism, toxicity)
• Adenoma, Liver Cell (chemically induced)
• Animals
• Animals, Newborn
• Carcinogenicity Tests
• Carcinogens (toxicity)
• DNA Adducts (biosynthesis)
• DNA Damage (drug effects)
• Epoxy Compounds (toxicity)
• Female
• Genes, ras (drug effects)
• Liver (metabolism)
• Liver Neoplasms (chemically induced, pathology)
• Male
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mutation
• Random Allocation