Human exposure to furan, an industrial intermediate and byproduct of combustion, is likely not accurately estimated.  Furan is found in heat treated foods and combustion mixtures such as cigarette smoke.  In mouse and rat studies, furan has been shown to be toxic to the liver and produce liver tumors.   Furan toxicity requires metabolic conversion to its reactive metabolite cis-2-butene-1,4-dial (BDA) by cytochrome P450 2E1.  BDA reacts with intracellular nitrogen and sulfur species to produce a myriad of metabolites.  Previously, we have identified furan metabolites in rodent urine as lysine adducts or crosslinks between lysine and cysteine.  Our long term goal is to explore the possible role furan plays in human disease, with the purpose of this work being to identify and quantify probable furan metabolites in human urine as a first step.  Urine obtained from smokers, before and after smoking cessation, and non-smokers was analyzed by LC-MS/MS.  Through the use of [13C615N2]-labeled internal standards, three metabolites were identified in all samples:  L-2-(acetylamino)-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-hexanoic acid (BDA-N-acetyl-lysine), N-acetyl-S-[1-(5-amino-5-carboxylpentyl)-1H-pyrrol-3-yl]-L-cysteine (N-acetyl-cysteine-BDA-Lys) and its sulfoxide (NAC-BDA-Lys sulfoxide).  Urinary levels of BDA-N-acetyl-lysine and N-acetyl-cysteine-BDA-Lys levels could not be quantified accurately due to analytical issues.  NAC-BDA-Lys sulfoxide levels were significantly elevated (ten-fold) in smokers compared to non-smokers and decreased after smoking cessation, indicating a link to cigarette smoke exposure.  These results indicate that NAC-BDA-Lys sulfoxide should be explored as a biomarker for furan exposure in humans.

Human urinary metabolites as possible biomarkers of exposure to furan

248th National Meeting (2014)

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