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) |
|---|---|
| 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 |
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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
Cite this
The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure. / Cupid, B. C.; Lightfoot, T. J.; Russell, D.; Gant, S. J.; Turner, P. C.; Dingley, K. H.; Curtis, K. D.; Leveson, S. H.; Turteltaub, Ken W; Garner, R. C.
In: Food and Chemical Toxicology, Vol. 42, No. 4, 04.2004, p. 559-569.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure
AU - Cupid, B. C.
AU - Lightfoot, T. J.
AU - Russell, D.
AU - Gant, S. J.
AU - Turner, P. C.
AU - Dingley, K. H.
AU - Curtis, K. D.
AU - Leveson, S. H.
AU - Turteltaub, Ken W
AU - Garner, R. C.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - Accelerator mass spectroscopy
KW - Adducts
KW - AFB, aflatoxin B
KW - Aflatoxin
KW - AMS, accelerator mass spectrometry
KW - B.w., body weight
KW - LLNL, Lawrence Livermore National Laboratory
KW - Low dose
KW - Risk assessment
UR - http://www.scopus.com/inward/record.url?scp=12144291342&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144291342&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2003.10.015
DO - 10.1016/j.fct.2003.10.015
M3 - Article
C2 - 15019179
AN - SCOPUS:12144291342
VL - 42
SP - 559
EP - 569
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
IS - 4
ER -