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DNA adducts derived from administration of acrylamide and glycidamide to mice and rats

Daniel R Doerge1, Gonçalo Gamboa da Costa, L Patrice McDaniel

  • 1Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA. ddoerge@nctr.fad.gov

Mutation Research
|January 26, 2005
PubMed

Insights

Acrylamide (AA), found in foods, forms glycidamide (GA) in the body, creating DNA adducts linked to cancer. This study supports a genotoxic mechanism for AA carcinogenicity, aiding risk assessment for human dietary exposure.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Food Safety

Background:

  • Acrylamide (AA) is an industrial chemical with known neurotoxic, mutagenic, and carcinogenic properties.
  • Recent detection of AA in common foods necessitates understanding risks from typical human exposures.
  • Glycidamide (GA), a metabolite of AA, is implicated in its toxic effects.

Purpose of the Study:

  • To investigate the formation of GA and GA-derived DNA adducts in vivo following AA exposure.
  • To compare the genotoxicity of AA and GA in rodent models.
  • To support a genotoxic mechanism for AA-induced carcinogenicity and inform risk assessment.

Main Methods:

  • Rodents (mice and rats) were dosed with acrylamide (AA) or glycidamide (GA).
  • Serum and tissue samples were analyzed for GA presence.
  • DNA adducts of adenine and guanine were quantified in various tissues.
  • Kinetics of adduct formation and accumulation were studied after single and repeated dosing.

Main Results:

  • Glycidamide (GA) was detected in serum and tissues of AA-dosed rodents.
  • GA-derived DNA adducts were found in all examined tissues, including both target and non-target organs.
  • Equimolar dosing of GA typically resulted in higher DNA adduct levels than AA.
  • Adduct formation kinetics correlated with known in vitro mutagenicity of AA and GA.

Conclusions:

  • Results strongly support a genotoxic mechanism for acrylamide carcinogenicity in rodents.
  • The formation of GA-derived DNA adducts is a key event in AA toxicity.
  • Kinetic and biomarker approaches may help extrapolate cancer risks from low human dietary exposures.

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