The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure
The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure
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DOI：
10.1016/j.fct.2003.10.015
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发表时间：
2004-04-01
影响因子：
4.3
通讯作者：
Garner, RC
中科院分区：
文献类型：
--
作者：
Cupid, BC;Lightfoot, TJ;Garner, RC
在人类和大鼠暴露于已知的饮食中相应量的碳-14标记的黄曲霉毒素B-1 （[C-14]AFB(1)）后，用加速器质谱法（AMS）研究了黄曲霉毒素B-1- dna和黄曲霉毒素B-1-白蛋白加合物的水平。本研究的目的是：(a)研究极低剂量AFB(1) （0.16 ng/kg-12.3 mug/kg）在大鼠体内DNA和蛋白质加合物形成的剂量依赖性；(b)在已知的、相关的人类暴露条件下测量AFB(1)-白蛋白和AFB(1)-DNA加合物的水平(c)研究大鼠对人类对AFB(1)-白蛋白和DNA加合物水平的推断。大鼠实验结果表明，在此剂量范围内，AFB(1)-白蛋白加合物和AFB(1)-DNA加合物的形成呈线性关系。所研究组织内加合物的形成顺序为肝>肾>结肠>肺=脾。同意的志愿者在接受结肠手术前大约3.5-7小时接受1杯（类似于15 ng/kg） [C-14]AFB(1)胶囊。人AFB(1)-白蛋白加合物的平均水平为38.8 +/- 19.55 pg [C-14]AFB(1)/mg白蛋白/杯AFB(1)/kg体重（b.w.），与大鼠的等效剂量（15 ng/kg） 42.29 +/- 7.13 pg [C-14]AFB（1)/mg白蛋白/杯AFB(1)/kg b.w.）无统计学差异。有证据表明，在极低剂量下，人结肠中形成AFB(1)- dna加合物。比较大鼠肝脏AFB(1)-DNA加合物和AFB(1)-白蛋白加合物水平的线性回归，发现它们在统计学上是相似的，这表明AFB(1)-白蛋白加合物水平是AFB(1)剂量学有用的生物标志物，可以反映靶组织中的DNA加合物水平。对[C-14]AFB(1)-DNA和[C-14]AFB(1)-白蛋白加合物进行了水解和高效液相色谱分析，证实了AMS测得的[C-14]来源于预期的[C-14]AFB(1)加合物。(C) 2003 Elsevier Ltd.版权所有。
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.