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

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.