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 language | English (US) |
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Pages (from-to) | 559-569 |
Number of pages | 11 |
Journal | Food and Chemical Toxicology |
Volume | 42 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2004 |
Externally published | Yes |
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