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.
Gaskell
Margaret
M
Cancer Biomarkers and Prevention Group, The Biocenter, University of Leicester, University Road, Leicester LE1 7RH, U.K. mg24@le.ac.uk
Jukes
Rebekah
R
Jones
Donald J L
DJ
Martin
Elizabeth A
EA
Farmer
Peter B
PB
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