Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice.

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 (MNRETs) 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 ¼ 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 ¼ 1.5 6 0.3 � 10 � 6 and 2.2 6 0.5 � 10 � 6 in females and males,