The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure

B. C. Cupid, T. J. Lightfoot, D. Russell, S. J. Gant, P. C. Turner, K. H. Dingley, K. D. Curtis, S. H. Leveson, Ken W Turteltaub, R. C. Garner

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46 Scopus citations

Abstract

The levels of aflatoxin B1-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 B1 ([14C]AFB1). The aims of the study were to: (a) investigate the dose-dependent formation of DNA and protein adducts at very low doses of AFB1 (0.16 ng/kg-12.3 μg/kg) in the rat; (b) measure the levels of AFB1-albumin and AFB1-DNA adducts at known, relevant exposures in humans (c) study rat to human extrapolations of AFB1-albumin and DNA adduct levels. The results in the rat showed that both AFB1-albumin adduct and AFB1-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 μg (∼15 ng/kg) of [14C]AFB1 in a capsule approximately ∼3.5-7 h prior to undergoing colon surgery. The mean level of human AFB1-albumin adducts was 38.8±19.55 pg [14C]AFB1/mg albumin/μg AFB1/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 [14C]AFB1/mg albumin/μg 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 AFB1-DNA adduct and AFB 1-albumin adduct levels in rat found them to be statistically similar suggesting that the level of AFB1-albumin adducts are useful biomarkers for AFB1 dosimetry and may reflect the DNA adduct levels in the target tissue. [14C]AFB1-DNA and [ 14C]AFB1-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [14C] measured by AMS was derived from the expected [14C]AFB1 adducts.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalFood and Chemical Toxicology
Volume42
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Keywords

  • Accelerator mass spectroscopy
  • Adducts
  • AFB, aflatoxin B
  • Aflatoxin
  • AMS, accelerator mass spectrometry
  • B.w., body weight
  • LLNL, Lawrence Livermore National Laboratory
  • Low dose
  • Risk assessment

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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    Cupid, B. C., Lightfoot, T. J., Russell, D., Gant, S. J., Turner, P. C., Dingley, K. H., Curtis, K. D., Leveson, S. H., Turteltaub, K. W., & Garner, R. C. (2004). The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure. Food and Chemical Toxicology, 42(4), 559-569. https://doi.org/10.1016/j.fct.2003.10.015