56287-13-9Relevant articles and documents
Simultaneous quantitation of N2,3-ethenoguanine and 1,N2-ethenoguanine with an immunoaffinity/gas chromatography/high-resolution mass spectrometry assay
Morinello,Ham,Ranasinghe,Sangaiah,Swenberg
, p. 327 - 334 (2001)
We have previously described an immunoaffinity/gas chromatography/electron capture negative chemical ionization high-resolution mass spectrometry (IA/GC/ECNCI-HRMS) assay for quantitation of the promutagenic DNA adduct N2,3-ethenoguanine (N2,3-εGua) in vivo. Here we present an expanded assay that allows simultaneous quantitation of its structural isomer, 1,N2-ethenoguanine (1,N2-εGua), in the same DNA sample. 1,N2-εGua and N2,3-εGua were purified together from hydrolyzed DNA using two immobilized polyclonal antibodies. GC/ECNCI-HRMS was used to quantitate the 3,5-bis(pentafluorobenzyl) (PFB) derivative of each adduct against an isotopically labeled analogue. Selected ion monitoring was used to detect the [M - 181]- fragments of 3,5-(PFB)2-N2,3-εGua and 3,5-(PFB)2-[13C4,15N 2]-N2,3-εGua and the [M - 201]- fragments of 3,5-(PFB)2-1,N2-εGua and 3,5-(PFB)2-[13C3]-1,N2-εGua. The demonstrated limits of quantitation in hydrolyzed DNA were 7.6 fmol of N2,3-εGua and 15 fmol of 1,N2-εGua in ～250 μg of DNA, which corresponded to 5.0 N2,3-εGua and 8.7 1,N2-εGua adducts/108 unmodified Gua bases, respectively. 1,N2-εGua was found to be the predominant ethenoguanine adduct formed in reactions of lipid peroxidation products with DNA. The respective ratios of 1,N2-εGua to N2,3-εGua were 5:1 and 38:1 when calf thymus DNA was treated with ethyl linoleate or 4-hydroxynonenal, respectively, under peroxidizing conditions. Only N2,3-εGua was detected in DNA treated with the vinyl chloride (VC) metabolite 2-chloroethylene oxide and in hepatocyte DNA from rats exposed to 1100 ppm VC for 4 weeks (6 h/day for 5 days/week). These data suggest that 1,N2-εGua plays a minor role relative to N2,3-εGua in VC-induced carcinogenesis, but that 1,N2-εGua may be formed to a larger extent from endogenous oxidative processes.
Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts.
Ruohola, Anne-Mari,Koissi, Niangoran,Andersson, Sanna,Lepistoe, Ilona,Neuvonen, Kari,Mikkola, Satu,Loennberg, Harri
, p. 1943 - 1950 (2007/10/03)
Reactions of 9-ethylguanine, 2'-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by (1)H and (13)C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH 7. In addition to these, an N(2)-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N(2)-carboxymethyl-1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N(2)-ethenoguanine (5a-c) and N(2),3-ethenoguanine adducts (4a-c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N(2)-(1,2,2,3-tetrahydroxypropano)(8) and 1,N(2)-(2-formyl-1,2,3-trihydroxypropano)(9) adducts, was observed.
Unequivocal Assignment of the Skeletal Structure of the Guanine-Glyoxal Adduct
Czarnik, Anthony W.,Leonard, Nelson J.
, p. 3514 - 3517 (2007/10/02)
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