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

Abstract

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.