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

Abstract

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 ([ 14C]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 μg/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 μg (∼15 ng/kg) of [ 14C]AFB 1 in a capsule 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 [ 14C]AFB 1/mg albumin/μg 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 [ 14C]AFB 1/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 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. [ 14C]AFB 1-DNA and [ 14C]AFB 1-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [ 14C] measured by AMS was derived from the expected [ 14C]AFB 1 adducts.