title: Development of a urinary biomarker of human exposure to deoxynivalenol.
abstract: 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 [14C]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 microCi/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 microg/kg/day and 0.3-1.4 microg/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.
authors.affiliation: Molecular Epidemiology Unit, Epidemiology and Health Services Research, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: F A
authors.initials: FA
authors.lastname: Meky
authors.forename: P C
authors.initials: PC
authors.lastname: Turner
authors.forename: A E
authors.initials: AE
authors.lastname: Ashcroft
authors.forename: J D
authors.initials: JD
authors.lastname: Miller
authors.forename: Y-L
authors.initials: YL
authors.lastname: Qiao
authors.forename: M J
authors.initials: MJ
authors.lastname: Roth
authors.forename: C P
authors.initials: CP
authors.lastname: Wild
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D002681:China; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004784:Environmental Monitoring / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014255:Trichothecenes / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D015415:Biomarkers; D014255:Trichothecenes; C007262:deoxynivalenol