Correlation between hemoglobin adducts and DNA adducts following acrylamide and glycidamide exposures in Fischer 344 rats and B6C3F1 mice

TOXI 63

Eden Tareke, etareke@nctr.fda.gov1, Mona I. Churchwell, mona.churchwell@fda.hhs.gov2, L. Patrice McDaniel2, Nathan C. Twaddle2, and Daniel R. Doerge, daniel.doerge@fda.hhs.gov2. (1) Division of Personalized Nutrition and Medicine, National Center Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, (2) Division of Biochemical Toxicology, NCTR, 3900 NCTR Road, Jefferson, AR 72079
Acrylamide is a neurotoxic, mutagenic, and carcinogenic industrial chemical and food contaminant. We have assessed the relationships between serum levels of acrylamide and its genotoxic metabolite glycidamide and the levels of hemoglobin and DNA adducts in mice and rats administered single or repeated doses of acrylamide or glycidamide. There were significant linear relationships between the area under the serum time-concentration curve (AUC) for glycidamide and both liver glycidamide DNA adducts and glycidamide hemoglobin adducts in rodents administered either acrylamide or glycidamide (0.1 mg/kg bw). There was no relationship between either the AUC for acylamide or acylamide hemoglobin adducts and liver glycidamide DNA adducts. There was also a significant linear relationship between steady-state levels of glycidamide hemoglobin adducts and liver glycidamide DNA adducts for repeat dosing with acrylamide (1-2 mg/kg bw/d). These results suggest that glycidamide hemoglobin adduct levels can predict glycidamide DNA adduct levels when DNA samples are not available.
 

Poster Presentations and Awards
6:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 104, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Chemical Toxicology

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006