N7- guanine

Some of the following adducts also have been characterized, although not all thoroughly adenosine (108,111). the 0 (87) and N7-guanine derivatives (86-88), phosphate (85) and adducts resulting from the further epoxidation of the 9-hydroxy B[a]P at the 4,5-position (67,68). 

Koivisto, P, Sorsa, M., Pacchierotti. F. Peltonen, K. (1997) - p.postlabelling/HPLC assay reveals an enantioselective adduct formation in N7 guanine residues in vivo after 1,3-butadiene inhalation exposure. Carcinogenesis. 18, 439-443... 

Tretyakova, N.Y, Sangaiah, R., Yen, T.Y. Swenberg, J.A. (1997c) Synthesis, characterization, and in vitro quantitation of N7-guanine adducts of diepoxy butane. Chem. Res. Toxicol., 10,779-785... 

The N7-guanine adduct (22) is a urinary excretion product derived from the reaction of sulfur mustard with DNA. It can be isolated from urine by SPE on C18. GC/MS analysis of the derivatized adduct was problematic. A sensitive method was developed for the underivatized compound using LC/ESI/MS/MS, monitoring the fragmentation MH+, m/z 256 —> [CH2CH2SCH2CH2OH]+, m/z 105 on a triple-sector quadrupole instrument (60). LC separation was on a C18 column eluted with water-acetonitrile-formic acid. The detection limit was 8pg injected (S/N 5 1), 0.2 ng/ml in urine. Rao et al. (61) also reported characterization by LC/ESI/MS but using 25 mM NH4HC03 in 20 % MeOH as eluent. 

Figure 24.12. Examples of DNA adducts and oxidized guanine nucleotide. (A) Benzo[a]pyrene-7,8-diol-9,10-epoxide-M-2 guanine adduct. (B) Aflatoxin epoxide N7 guanine adduct. (C) 8-Oxoguanine is commonly produced by reactive oxygen species, dR = deoxyribose.

Figure 5 Two types of mutations (G->T transversion and C—s-T transition) resulting from the AFBl-N7-guanine adduct [8,9-dihydro-8-(N7 guanyl)-9-hydroxyaflatoxin] Bl. Newly synthesized DNA strand dashed boxes.

Sulfur mustard has been shown to react with nucleic acid components and the N7-guanine adduct studied by several techniques (Rao et al., 2002). 

McCoull, K.D., Rindgen, D., Blair, I.A., and Penning, T.M. (1999) Synthesis and characterization of polycyclic aromatic hydrocarbon o-quinone depurinating N7-guanine adducts. Chem. Res. 

Formation of depurinating N3 adenine and N7 guanine adducts by MCF-10F cells cultured in the presence of 4-hydroxyestradiol. Int. J. Cancer, 120, 1821-1824. 

The possible coordination sites of the studied dinucleotides are guanine N7(G-N7), guanine N1 and cytosine N3 (C - N3) (25). In our conditions (stoichiometry of the reaction and pH) G-Nl coordination is very unlikely (11). For several 5 - ( mono or bis complexes, N7 coordination induces a characteristic... 

Intercalation between complementary intrastrand nucleobases (type III) shows an intrahelical disposition of (i) in the case of A-T chelation, bindings appear at Ni adenine and N3 thymine (ii) in the case of the G-C chelation, the bindings appear at Ni guanine and N3 cytosine (Figure 7.6). The first approach is characteristic for Hg ", and the second for Cu " and Cd ". The binding is also possible to N7 guanine, N3 cytosine and to O from Cg, respectively C2. 

Malayappan, B. et (2010) Quantitative high-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis of bis-N7-guanine DNA-DNA cross-links in white blood cells of cancer patients receiving cyclophosphamide therapy. Anal. Chem., 82 (9), 3650-3658. 

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