title: Metabolomic profiles of current cigarette smokers.
abstract: Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked two cigarettes 1 h apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Ping-Ching
authors.initials: PC
authors.lastname: Hsu
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Renny S
authors.initials: RS
authors.lastname: Lan
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Brasky
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.|Department of Biochemistry, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC.
authors.forename: Habtom W
authors.initials: HW
authors.lastname: Ressom
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Loffredo
authors.affiliation: Battelle, Public Health Center for Tobacco Research, Baltimore, Maryland.
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Pickworth
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008610:Menthol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005965:Glucuronates; D008610:Menthol; C044963:menthol glucuronide
keywords: UHPLC-QTOF-MS; menthol; metabolomics; plasma; smokers