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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.