Development of a urinary biomarker of human exposure to deoxynivalenol

被引:144
作者
Meky, FA
Turner, PC
Ashcroft, AE
Miller, JD
Qiao, YL
Roth, MJ
Wild, CP [1 ]
机构
[1] Univ Leeds, Mol Epidemiol Unit, Epidemiol & Hlth Serv Res, Sch Med, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Leeds, Dept Biochem & Mol Biol, Leeds LS2 9JT, W Yorkshire, England
[3] Carleton Univ, Dept Chem, Ottawa, ON K1S 5B6, Canada
[4] Chinese Acad Med Sci, Dept Epidemiol, Inst Canc, Beijing 100021, Peoples R China
[5] NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA
关键词
deoxynivalenol; biomarkers; human exposure;
D O I
10.1016/S0278-6915(02)00228-4
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Deoxynivalenol (DON) is a mycotoxin frequently found as a contaminant of cereal crops and may be etiologically associated with adverse health effects in developing countries where considerable quantities of contaminated crops are consumed. We investigated the metabolism of DON in rats as a basis to establish methodology for a candidate biomarker of human exposure to this toxin and tested this methodology on urine samples from a potentially highly exposed population. Sprague-Dawley rats received a single dose of [C-14]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 muCi/kg) and the distribution of DON in body fluids was investigated over 72 h. DON and its metabolites were detectable in the plasma of rats with the highest levels at 8 h, at which time approximately 9% was bound to plasma protein. A total of 37% of the administered DON was excreted in the urine and DON-glucuronide was implicated as the major urinary metabolite based on reverse-phase HPLC analysis of beta-glucuronidase- and sulphatase-treated samples. An immunoaffinity column (IAC)-HPLC method was subsequently developed to measure urinary metabolites, with a view to establishing a urine-based human biomarker. Urine samples were collected from female inhabitants of Linxian County, China, a high risk region for oesophageal cancer (OC) and an area of potentially high DON exposure, and Gejiu, a low risk region in China. DON was detected in all 15 samples following beta-glucuronidase treatment and IAC enrichment with the identity of DON being confirmed by mass spectrometry. The mean levels of DON from the suspected high and low exposure regions of China were 37 ng/ml (range 14-94 ng/ml) and 12 ng/ml (range 4-18 ng/ml), respectively. This is estimated to correspond to daily exposures of 1.1-7.4 mug/kg/day and 0.3-1.4 mug/kg/day, respectively. This is the first reported measurement of a urinary biomarker for DON in both animals and humans and should facilitate epidemiological studies of disease associations with this mycotoxin. (C) 2003 Elsevier Science Ltd. All rights reserved.
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收藏
页码:265 / 273
页数:9
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