This article is a US Government work, and, as such, is in the public domain in the United States of America.
Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice†
Version of Record online: 14 JUN 2005
Published 2005 Wiley-Liss, Inc.
Environmental and Molecular Mutagenesis
Volume 47, Issue 1, pages 6–17, January 2006
How to Cite
Manjanatha, M. G., Aidoo, A., Shelton, S. D., Bishop, M. E., McDaniel, L. P., Lyn-Cook, L. E. and Doerge, D. R. (2006), Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice. Environ. Mol. Mutagen., 47: 6–17. doi: 10.1002/em.20157
- Issue online: 6 JAN 2006
- Version of Record online: 14 JUN 2005
- Manuscript Accepted: 5 MAY 2005
- Manuscript Revised: 29 MAR 2005
- Manuscript Received: 18 FEB 2005
- National Institute for Environmental Health Sciences/National Toxicology Program
- Big Blue;
- cII mutations
The recent discovery of acrylamide (AA), a probable human carcinogen, in a variety of fried and baked starchy foods has drawn attention to its genotoxicity and carcinogenicity. Evidence suggests that glycidamide (GA), the epoxide metabolite of AA, is responsible for the genotoxic effects of AA. To investigate the in vivo genotoxicity of AA, groups of male and female Big Blue (BB) mice were administered 0, 100, or 500 mg/l of AA or equimolar doses of GA, in drinking water, for 3–4 weeks. Micronucleated reticulocytes (MN-RETs) were assessed in peripheral blood within 24 hr of the last treatment, and lymphocyte Hprt and liver cII mutagenesis assays were conducted 21 days following the last treatment. Further, the types of cII mutations induced by AA and GA in the liver were determined by sequence analysis. The frequency of MN-RETs was increased 1.7–3.3-fold in males treated with the high doses of AA and GA (P ≤ 0.05; control frequency = 0.28%). Both doses of AA and GA produced increased lymphocyte Hprt mutant frequencies (MFs), with the high doses producing responses 16–25-fold higher than that of the respective control (P ≤ 0.01; control MFs = 1.5 ± 0.3 × 10−6 and 2.2 ± 0.5 × 10−6 in females and males, respectively). Also, the high doses of AA and GA produced significant 2–2.5-fold increases in liver cII MFs (P ≤ 0.05; control MFs = 26.5 ± 3.1 × 10−6 and 28.4 ± 4.5 × 10−6). Molecular analysis of the mutants indicated that AA and GA produced similar mutation spectra and that these spectra were significantly different from that of control mutants (P ≤ 0.001). The predominant types of mutations in the liver cII gene from AA- and GA-treated mice were G:CT:A transversions and −1/+1 frameshifts in a homopolymeric run of Gs. The results indicate that both AA and GA are genotoxic in mice. The MFs and types of mutations induced by AA and GA in the liver are consistent with AA exerting its genotoxicity in BB mice via metabolism to GA. Environ. Mol. Mutagen., 2006. Published 2005 Wiley-Liss, Inc.