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

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 ([C-14]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 mug/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 I mug (similar to15 ng/kg) of [C-14]AFB(1) in a capsule approximately similar to3.5-7 h prior to undergoing colon surgery. The mean level of human AFB(1)-albumin adducts was 38.8 +/- 19.55 pg [C-14]AFB(1)/mg albumin/mug 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 [C-14]AFB(1)/mg albumin/mug 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. [C-14]AFB(1)-DNA and [C-14]AFB(1)-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [C-14] measured by AMS was derived from the expected [C-14]AFB(1) adducts. (C) 2003 Elsevier Ltd. All rights reserved.