Analysis of ethenoguanine adducts in human urine using high performance liquid chromatography–tandem mass spectrometry

• Published in: Toxicology letters Vol. 134; no. 1; pp. 71 - 77
• Main Authors: Gonzalez-Reche, Luis Mariano, Koch, Holger Martin, Weiß, Tobias, Müller, Johannes, Drexler, Hans, Angerer, Jürgen
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.08.2002; Amsterdam Elsevier Science
• Subjects: Adult; Biological and medical sciences; Biological monitoring; Biomarkers - urine; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Chromatography, High Pressure Liquid - methods; DNA Adducts - urine; Environmental Monitoring - methods; Etheno adduct; Ethenoguanine; Female; Gas Chromatography-Mass Spectrometry; General population; Guanine - analogs & derivatives; Guanine - urine; Humans; Male; Medical sciences; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods; Tumors; Urine; Urine; Etheno adduct; General population; Biological monitoring; Ethenoguanine; Human; Biological fluid; Coupled method; HPLC chromatography; Occupational exposure; Purine base derivatives; DNA; Mass spectrometry MS/MS; Ethylene(chloro); Molecular adduct; Occupational medicine
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(02)00165-0

Several chemical carcinogens, such as vinyl chloride and ethyl carbamate, can react with DNA to form etheno-adducts in vitro and in vivo, which can be repaired through the base excision repair pathway, and then excreted with the urine. A specific and sensitive method, based on high performance liquid chromatography electrospray ionization tandem mass spectrometry, was developed for the detection of ethenoguanines (1,N2-ethenoguanine and its isomer N2,3 ethenoguanine) in urine. Urine samples were obtained from13 healthy subjects not occupationally exposed to industrial chemicals. A confirmatory GC/MS method was also applied. Ethenoguanine isomers excreted with the urine were in the low nmol/l range (<0.3–8 nmol/l). Since occupational exposure to chemicals that may form etheno-adducts can be ruled out, endogenously produced intermediates, such as 2,3-epoxy-4-hydroxynonanal, may be responsible for the formation of etheno-adducts in human DNA. The background level of the general population has to be taken into account, especially in the investigation of persons occupationally exposed to etheno-adduct forming chemicals.