Abundant Rodent
Furan-Derived Urinary Metabolites
Are Associated with Tobacco Smoke Exposure in Humans
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Abstract
Furan, a possible human carcinogen,
is found in heat treated foods
and tobacco smoke. Previous studies have shown that humans are capable
of converting furan to its reactive metabolite, <i>cis</i>-2-butene-1,4-dial (BDA), and therefore may be susceptible to furan
toxicity. Human risk assessment of furan exposure has been stymied
because of the lack of mechanism-based exposure biomarkers. Therefore,
a sensitive LC-MS/MS assay for six furan metabolites was applied to
measure their levels in urine from furan-exposed rodents as well as
in human urine from smokers and nonsmokers. The metabolites that result
from direct reaction of BDA with lysine (BDA-<i>N</i><sup>α</sup>-acetyllysine) and from cysteine-BDA-lysine cross-links
(<i>N</i>-acetylcysteine-BDA-lysine, <i>N</i>-acetylcysteine-BDA-<i>N</i><sup>α</sup>-acetyllysine, and their sulfoxides)
were targeted in this study. Five of the six metabolites were identified
in urine from rodents treated with furan by gavage. BDA-<i>N</i><sup>α</sup>-acetyllysine, <i>N</i>-acetylcysteine-BDA-lysine,
and its sulfoxide were detected in most human urine samples from three
different groups. The levels of <i>N</i>-acetylcysteine-BDA-lysine
sulfoxide were more than 10 times higher than that of the corresponding
sulfide in many samples. The amount of this metabolite was higher
in smokers relative to that in nonsmokers and was significantly reduced
following smoking cessation. Our results indicate a strong relationship
between BDA-derived metabolites and smoking. Future studies will determine
if levels of these biomarkers are associated with adverse health effects
in humans