Thymine glycols

There is always interest in the photochemistry of the pyrimidine nucleic acid bases and related simple pyrimidinones, due to its importance in genetic mutation. In addition to damaging DNA, photo-induced reactions may also repair the damage, as in the reduction, by FADH, of the thymine glycol 64 back to thymine <06JACS10934>. Another report related to repair of DNA involved a model study, by means of the linked dimer 65, of the involvement of tryptophan in the electron-transfer leading to reversion of thymine oxetane adducts <06OBC291>. 

Huttermann J, Ward JF, Myers LS Jr (1971) Electron spin resonance studies of free radicals in irradiated single crystals of 5-methylcytosine. Int J Radiat PhysChem 3 117-129 Huttermann J, Ohlmann J, Schaefer A, Gatzweiler W (1991) The polymorphism of a cytosine anion studied by electron paramagnetic resonance spectroscopy. Int J Radiat Biol 59 1297-1311 Hwang CT, Stumpf CL, Yu Y-Q, Kentamaa HI (1999) Intrinsic acidity and redox properties of the adenine radical cation. Int J Mass Spectrom 182/183 253-259 Ide H, Otsuki N, Nishimoto S, Kagiya T (1985) Photoreduction of thymine glycol sensitized by aromatic amines in aqueous solution. J Chem Soc Perkin Trans 2 1387-1392 Idris Ali KM, Scholes G (1980) Analysis of radiolysis products of aqueous uracil + N20 solutions. J Chem Soc Faraday Trans 176 449-456... 

Nishimoto S, Ide H, Otsuki N, Nakamichi K, Kagiya T (1985) Radiation-induced reduction of thymine derivatives in aqueous solution. Part 4. Promoted transformation of thymine glycol into thymine by aromatic amines and low-valent transition metal salts. J Chem Soc Perkin Trans 2 1127-1134... 

Wardman P, Dennis MF, Everett SA, Patel KB, Stratford MRL, Tracy M (2003) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones the kinetic basis for hypoxia-selective, bioreductive drugs. Biochem Soc Symp 61 171-194 Warman JM, de Haas MP, Hummel A, van Lith D, VerberneJB, Loman H (1980) A pulse radiolysis conductivity study of frozen aqueous solutions of DNA. Int J Radiat Biol 38 459-459 Warman JM, de Haas MP, Rupprecht A (1996) DNA a molecular wire Chem Phys Lett 249 319-322 Warters RL, Lyons BW (1992) Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. Radiat Res 130 309-318 Warters RL, Hofer KG, Harris CR, Smith JM (1977) Radionuclide toxicity in cultured mammalian cells Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12 389-407 Weiland B, Huttermann J (1998) Free radicals from X-irradiated, dry and hydrated lyophilized DNA as studies by electron spin resonance spectroscopy analysis of spectral components between 77 K and room temperature. Int J Radiat Biol 74 341-358 Weinfeld M, Soderlind K-JM (1991) 32P-Postlabeling detection of radiation-induced DNA-damage identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

Pouget J-P, Ravanat J-L, DoukiT, Richard M-J, Cadet J (1999) Use of the comet assay to measure DNA damage in cells exposed to photosensitizers and gamma radiation. J Chim Phys 96 143-146 Rajagopalan R, Melamede RJ, Laspia MF, Erlanger BF, Wallace SS (1984) Properties of antibodies to thymine glycol, a product of the radiolysis of DNA. Radiat Res 97 499-510... 

Weinfeld M, Soderlind K-JM (1991) 32P-postlabeling detection of radiation-induced DNA-damage Identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

L. N. Daniel, Y. Mao, T.-C. L. Wang, C. J. Markey, S. P. Markey, X. Shi, and U. Saffiotti, DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro, Environ. Res. 71, 60-73 (1995). 

Oxoguanine Thymine glycol Cytosine hydrate FaPy-G FaPy-A... 

In vivo, thymine glycol may be one of the most interesting biomarkers of non-enzymatic aromatic hydroxylation, for it can be detected by non-invasive analysis of urine [46], As shown in the upper part of Fig. 2, the one-electron reductive cleavage observed in the Fenton reaction can be extended to alkyl hydroperoxides, ROOH, yielding alkoxyl radicals, RO , whose oxidizing power, although smaller than that of OH , is still considerable [20,24,47] ... 

A carcinogen that can generate free radicals can, in principle, bring about the formation of modified bases such as thymine glycols in cellular DNA [128], but radicals can also cause single-strand and double-strand DNA breaks [129,130]. Critically however many radical-induced DNA damaging events can be abolished by free radical scavengers [131]. 

K5. Kaneko, M., and Leadon, S. A., Production of thymine glycols in DNA by N-hydroxy-2-naphthylamine as detected by monoclonal antibody. Cancer Res. 46, 71-75 (1986). 

On p. 590 we discuss briefly the mechanism of the Os04-alkene-L reaction. The reaction in which cis diols R(OH)2 react with 0s03py2 is thought to proceed via nucleophilic attack by the diol on osmium pyridine species. This is consistent with kinetic data and also with l80-labelling experiments on thymine glycols which demonstrated that there was no C—O bond cleavage.530... 

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