Faculty Collaboration Database

Abundant Rodent Furan-Derived Urinary Metabolites Are Associated with Tobacco Smoke Exposure in Humans. Chem Res Toxicol 2015 Jul 20;28(7):1508-16

Date

06/27/2015

Pubmed ID

26114498

Pubmed Central ID

PMC5473163

DOI

10.1021/acs.chemrestox.5b00189

Scopus ID

2-s2.0-84937677285 (requires institutional sign-in at Scopus site)   30 Citations

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, cis-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-N(α)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcysteine-BDA-lysine, N-acetylcysteine-BDA-N(α)-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-N(α)-acetyllysine, N-acetylcysteine-BDA-lysine, and its sulfoxide were detected in most human urine samples from three different groups. The levels of N-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.

Author List

Grill AE, Schmitt T, Gates LA, Lu D, Bandyopadhyay D, Yuan JM, Murphy SE, Peterson LA

Author

Thaddeus Schmitt MD Assistant Professor in the Emergency Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aldehydes
Animals
Biomarkers
Chromatography, High Pressure Liquid
Female
Furans
Humans
Male
Mice
Rats
Rats, Inbred F344
Smoking
Tandem Mass Spectrometry