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Abundant rodent furan-derived urinary metabolites are associated with tobacco smoke exposure in humans.

Grill AE; Schmitt T; Gates LA; Lu D; Bandyopadhyay D; Yuan J-M; Murphy SE; Peterson LA

Chem Res Toxicol 2015 Jul; 28(7):1508-1516

https://doi.org/10.1021/acs.chemrestox.5b00189

20047902

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(a)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcysteine-BDA-lysine, N-acetylcysteine-BDA-N(a)-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(a)-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.

Furans; Carcinogens; Heat; Heat treatment; Food; Tobacco smoke; Metabolic effects; Metabolic activation; Toxic effects; Toxins; Exposure levels; Risk factors; Biomarkers; Urine; Urinalysis; Animals; Laboratory animals; Humans; Men; Women; Smoking

Lisa A. Peterson, University of Minnesota, Cancer and Cardiovascular Research Building, Room 2-126, 2231 Sixth Street S.E., Minneapolis, MN, 55455

CRTOEC

20150720

Journal Article

peter431@umn.edu

Grant

2015

Grant-Number-T42-OH-008434

7

0893-228X

Chemical Research in Toxicology

MN; PA

University of Minnesota Twin Cities