title: Elevated urinary levels of carcinogenic N-nitrosamines in patients with urinary tract infections measured by isotope dilution online SPE LC-MS/MS.
abstract: N-nitrosamines (NAms) are well-documented for their carcinogenic potential. Human exposure to NAms may arise from the daily environment and endogenous formation via the reaction of secondary amines with nitrites or from bacteria infection. We describe the use of isotope dilution online solid-phase extraction (SPE) LC-MS/MS to quantify nine NAms in human urine. This method was validated and further applied to healthy subjects and patients with urinary tract infection (UTI). N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine (NPYR) and N-nitrosomorpholine (NMOR) were analyzed with an APCI source, while N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPIP), N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were quantified with an ESI source, due to their effect on the sensitivity and chromatography. NDMA was the most abundant N-nitrosamine, while NDPhA was firstly identified in human. UTI patients had three to twelve-fold higher concentrations for NDMA, NPIP, NDEA, NMOR and NDBA in urine than healthy subjects, and the NAms were significantly decreased after antibiotics treatment. NDMA concentrations were also significantly correlated with the pH value, leukocyte esterase activity or nitrite in urines of UTI patients. Our findings by online SPE LC-MS/MS method evidenced that UTI patients experienced various NAms exposures, especially the potent carcinogen NDMA, which was likely induced by bacteria infection.
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Chiung-Wen
authors.initials: CW
authors.lastname: Hu
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Shih
authors.affiliation: Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Hung-Hsin
authors.initials: HH
authors.lastname: Liu
authors.affiliation: Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan; School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Occupational Safety and Health, Chung Shan Medical University, Taichung 402, Taiwan; Department of Occupational Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: chaomurong@gmail.com.
authors.forename: Mu-Rong
authors.initials: MR
authors.lastname: Chao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000652:urine*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002273:Carcinogens / Q000032:analysis*; D002853:Chromatography, Liquid; D006801:Humans; D007554:Isotopes; D008875:Middle Aged; D009573:Nitrites / Q000652:urine; D009602:Nitrosamines / Q000652:urine*; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000652:urine*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002273:Carcinogens; D007554:Isotopes; D009573:Nitrites; D009602:Nitrosamines; C021443:leukocyte esterase; D002265:Carboxylic Ester Hydrolases
keywords: LC–MS/MS; N-nitrosamines; N-nitrosodimethylamine; Online solid-phase extraction; Urinary tract infection