Analysis of ethenoguanine adducts in human urine using high performance liquid chromatography-tandem mass spectrometry.
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 from 13 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.
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Friedrich-Alexander University Erlangen-Nuremberg, Schillerstr. 25, D-91054 Erlangen, Germany.
Luis Mariano
LM
Gonzalez-Reche
Holger Martin
HM
Koch
Tobias
T
Weiss
Johannes
J
Müller
Hans
H
Drexler
Jürgen
J
Angerer
D000328:Adult; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018736:DNA Adducts / Q000652:urine*; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D015415:Biomarkers; D018736:DNA Adducts; C071372:N(2),3-ethanoguanine; C085534:1,(N2)-ethenoguanine; D006147:Guanine