The formation of AFB(1)-macromolecular adducts in rats and humans at dietary levels of exposure

Food Chem Toxicol. 2004 Apr;42(4):559-69. doi: 10.1016/j.fct.2003.10.015.


The levels of aflatoxin B(1)-DNA and aflatoxin B(1)-albumin adducts were investigated by accelerator mass spectrometry (AMS) in humans and rats following exposure to a known, dietary relevant amount of carbon-14 labeled aflatoxin B(1) ([(14)C]AFB(1)). The aims of the study were to: (a) investigate the dose-dependent formation of DNA and protein adducts at very low doses of AFB(1) (0.16 ng/kg-12.3 microg/kg) in the rat; (b) measure the levels of AFB(1)-albumin and AFB(1)-DNA adducts at known, relevant exposures in humans (c) study rat to human extrapolations of AFB(1)-albumin and DNA adduct levels. The results in the rat showed that both AFB(1)-albumin adduct and AFB(1)-DNA adduct formation were linear over this wide dose range. The order of adduct formation within the tissues studied was liver>kidney>colon>lung=spleen. Consenting volunteers received 1 microg ( approximately 15 ng/kg) of [(14)C]AFB(1) in a capsule approximately approximately 3.5-7 h prior to undergoing colon surgery. The mean level of human AFB(1)-albumin adducts was 38.8+/-19.55 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg body weight (b.w.), which was not statistically different to the equivalent dose in the rat (15 ng/kg) 42.29+/-7.13 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg b.w. There was evidence to suggest the formation of AFB(1)-DNA adducts in the human colon at very low doses. Comparison of the linear regressions of hepatic AFB(1)-DNA adduct and AFB(1)-albumin adduct levels in rat found them to be statistically similar suggesting that the level of AFB(1)-albumin adducts are useful biomarkers for AFB(1) dosimetry and may reflect the DNA adduct levels in the target tissue. [(14)C]AFB(1)-DNA and [(14)C]AFB(1)-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [(14)C] measured by AMS was derived from the expected [(14)C]AFB(1) adducts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxin B1 / analysis
  • Aflatoxin B1 / metabolism
  • Aflatoxin B1 / toxicity*
  • Aflatoxins / analysis
  • Aflatoxins / metabolism*
  • Albumins / analysis
  • Albumins / metabolism*
  • Animals
  • Carcinogens / administration & dosage
  • Carcinogens / metabolism
  • Carcinogens / toxicity*
  • DNA Adducts / metabolism*
  • Diet*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mass Spectrometry
  • Rats
  • Rats, Inbred F344
  • Risk Assessment
  • Scintillation Counting


  • Aflatoxins
  • Albumins
  • Carcinogens
  • DNA Adducts
  • aflatoxin-albumin adduct
  • Aflatoxin B1