8-Hydroxy-20-deoxyguanosine

The most commonly measured product of DNA oxidation is 8-hydroxy-deoxyguanosine (8-OHdG). This product is usually measured by HPLC methods however, the recent development of commercial ELISA kits is expanding research in this area. 

Beehler, B.C., Przybyszewski, J., Box, H.B. Kulesz-Martin, F. (1992) Formation of 8-hydroxy-deoxyguanosine within DNA of mouse keratinocytes exposed in culture to UVB and H2O2. Carcinogenesis, 13, 2003-2007... 

EDRF endothelium-derived relaxing 8-OHdG 8-hydroxy-deoxyguanosine... 

Production of ROS, factors involved in the aging process (Finkel and Holbrook, 2000), is elevated in AD brain and may be an important cause of AD (Martins et al., 1986). Elevated levels of oxicUzed hpids (lipid peroxidation, maloncUaldehyde, 4-hydroxynonenal) (Markesbery and Carney, 1999), proteins (advanced glycation end product mocUfications, tyrosine nitration) (Good et al., 1996 Takeda et al., 1998), and nucleic acids (8-hydroxy-deoxyguanosine) have been documented in AD brains (Lyras et al., 1997). Mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex... 

Weiss, D.J. and Lunte, C.E. (2000). Detection of a urinary biomaker for oxidative DNA damage 8-hydroxy-deoxyguanosine by capillary electrophoresis with electrochemical detection. Electrophoresis 21, 2080-5. 

Ichinose, T. et al.. Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles. Carcinogenesis, 18 (1), 185, 1997. 

Sumida, S., Doi, T., Sakurai, M., Yoshioka, Y., and Okamura, K., Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans. Free Radic. Res., 21, 607, 1997. 

Tardieu, D. Jaeg, J.P. Deloly, A. Carpet, E.D. Cadet, J. Petit, C.R. The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates apoptosis in mucosa during early colonic inflammation in rats. Carcinogenesis 2000, 21 (5), 973-976. 

The levels of 8-hydroxy-deoxyguanosine which were found to be elevated in the hippocampus and frontal cortex of rats treated with kainic acid (10 mg/kg) were significantly (P <0.05) reduced in animals co-treated with 10 mg melatonin/kg (Tang et al. 1998). 

Tile ID and 2D NMR experiments for 5-aza-7-deaza-2 -deoxyguanosine concluded that the oxo-amino tautomer 59a is preferable in DMSO-dg whereas the oxo-imino form 59b dominates in D2O (87JOC5136). Evidence for the hydroxy-imino tautomer 59c was not found. Poor solubility of the parent compound, 5-aza-7-deazaguanine (60) did not allow study of its tautomerism, but the pK values of protonation and deprotonation for 60 are identical with those for 59. 

A method has been reported for the quantification of the DNA oxidation products, 8-hydroxy-2 -deoxyguanosine (8-OH-dG), 8-hydroxy-2 -deoxyadenosine (8-OH-dA), 5-hydroxymethyl-2-deoxyuridine (HMDU), thymidine glycol (TG) and 2-hydroxy-2 -deoxyadenosine (2-OH-dA) [37], The HPLC system employed consisted of a 2.0 X 250 mm Cig column and gradient elution from waterimethanol, (94 6) to (10 90) over 28 min, at a flow rate of 200 tilmin ... 

Figure 5.62 Product-ion MS-MS spectra of the molecular ions from 8-hydroxy-2 -deoxyguanosine, obtained by (a) positive, and (b) negative ionization. Reprinted by permission of Elsevier Science from Comparison of negative- and positive-ion electrospray tandem mass spectrometry for the liquid chromatography-tandem mass spectrometry analysis of oxidized deoxynucleosides , by Hua, Y., Wainhaus, S. B., Yang, Y., Shen, L., Xiong, Y., Xu, X., Zhang, F. Bolton, J. L. and van Breemen, R. B., Journal of the American Society for Mass Spectrometry, Vol. 12, pp. 80-87, Copyright 2000 by the American Society for Mass Spectrometry.

This method was applied to the determination of these oxidized nucleosides in salmon testes using [ Cio, N5]-8-hydroxy-2 -deoxyguanosine (L-8-OH-dG) as the internal standard (Figure 5.65). Four of the oxidized products were below the limits of detection of the method, while the concentration of 8-OH-dG was determined to be 0.93 ppb. 

Lodovici M, Aiolli S, Monserrat C, et al. 1994. Effect of mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enz5mies in rat liver. J Environ Pathol Toxicol and Oncol 13 163-168. 

Adachi, S., Takemoto, K., Hirosuc, T. and Hosogai, Y. (1993). Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2 -deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets. Carcinogenesis 14, 265-268. 

Lu, L.J.W., Tasake, F., Hokanson, J.A. and Kohda, K. (1991). Detection of 8-hydroxy-2 -deoxyguanosine in deoxyribonucleic acid by the P-postlabelling method. Chem. Pharm. Bull. 39, 1880-1882. 

Shigenaga, M.K., Park, J.W., Cundy, K.C., Cimeno, C.J. and Ames, B.N. (1990). In pim oxidative DNA damage, measurement of 8-hydroxy-2 -deoxyguanosine in DNA and urine by high-performance liquid chromatography with electrochemical detection. Meth. Enzymol. 186, 521-530. 

Bodell, W. J. Ye, Q. Pathak, D. N. Pongracz, K. Oxidation of eugenol to form DNA adducts and 8-hydroxy-2 -deoxyguanosine role of quinone methide derivative in DNA adduct formation. Carcinogenesis 1998, 19, 437 143. 

C17H16N3OPtS+- 2 C19H24N8O10P-x 2 -Deoxycytidylyl-(3 — 5 )-2 -deoxyguanosine-2-hydroxy- CPGTPH 43 373... 

Matsui, M. et al., The role of oxidative DNA damage in human arsenic carcinogenesis Detection of 8-hydroxy-2 -deoxyguanosine in arsenic-related Bowen s disease, J. Invest. Dermatol., 113, 26, 1999. 

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