Identification and characterization of (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate, a novel DNA adduct formed by benzene metabolites.
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.
Cancer Biomarkers and Prevention Group, The Biocenter, University of Leicester, University Road, Leicester LE1 7RH, U.K. mg24@le.ac.uk
Margaret
M
Gaskell
Rebekah
R
Jukes
Donald J L
DJ
Jones
Elizabeth A
EA
Martin
Peter B
PB
Farmer
D000818:Animals; D001554:Benzene / Q000378:metabolism* / Q000633:toxicity; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis*; D003848:Deoxyguanine Nucleotides / Q000032:analysis* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
C469784:(3'',4''-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate; D018736:DNA Adducts; D003848:Deoxyguanine Nucleotides; C034009:2'-deoxyguanosine 3'-phosphate; D004247:DNA; D001554:Benzene