Identification and characterization of (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate, a novel DNA adduct formed by benzene metabolites

Chem Res Toxicol. 2002 Aug;15(8):1088-95. doi: 10.1021/tx0255368.

Abstract

Reaction of 2'-deoxyguanosine 3'-monophosphate with mixtures of the benzene metabolites p-benzoquinone (p-BQ) and hydroquinone (HQ) in an aqueous solution at pH 6.0 gave two main products which were isolated from the reaction mixture using reversed-phase HPLC and characterized using UV spectroscopy, negative ion electrospray mass spectrometry, and (1)H NMR. Variation of the ratio of p-BQ to HQ in the reaction mixture caused an increase in yield of one of the products. The two products were identified as (3"-hydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate and a new product, not previously characterized, (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate. Similar products were isolated from identical reactions with 2'-deoxyguanosine. Reaction of calf thymus DNA with HQ and p-BQ (1:1, w/w) resulted in four main products as identified by (32)P-postlabeling coupled with HPLC. The relative abundances of these adducts were 9%, 60%, 27%, and 4%, respectively. Co-chromatography of (32)P-postlabeled (3"-hydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate and (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate with the (32)P-postlabeled adducted calf thymus DNA identified these as the two minor products of the calf thymus DNA reaction.

MeSH terms

  • Animals
  • Benzene / metabolism*
  • Benzene / toxicity
  • Cattle
  • Chromatography, High Pressure Liquid
  • DNA / drug effects
  • DNA Adducts / analysis*
  • Deoxyguanine Nucleotides / analysis*
  • Deoxyguanine Nucleotides / metabolism
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • (3'',4''-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate
  • DNA Adducts
  • Deoxyguanine Nucleotides
  • 2'-deoxyguanosine 3'-phosphate
  • DNA
  • Benzene