5-Hydroxymethyl uracil

Hydroxymethyl-2 -deoxyuridine 5-Hydroxymethyl uracil 5-Hydroxymethyl-2 -deoxyuridine in DNA... 

Frenkel K, Cummings A, Solomon J, Cadet J, Steinberg JJ, Teebor GW (1985) Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of y-irradiated cells. Biochemistry... 

Faure, H., Mousseau, M., Cadet, J., Guimier, C., Tripier, M., Hida, H. and Favier, A. Urine 8-o.xo-7,8-dihydro-2-deoxyguanosine vs. 5-(hydroxymethyl) uracil as DNA oxidation marker in adriamycin-treated patients. Free Rad Res, 28, 1998, 377-382. 

Thymine (T) Cytosine (C) Adenine (A) Guanine 5-Hydroxymethyl-uracil (HMU) 6-Methylamino-purine (HMA)... 

Figure 3. OH radical-induced degradation of thymine. Oxidation involves either OH addition to the C5-06 double bond or OH-mediated hydrogen abstraction from the methyl group. Molecular oxygen then adds to the resulting carbon-centered radicals. This reaction yields hydroperoxide that further evolves into stable products, such as thymidine glycol (ThdGly), 5-hydroxymethyl-uracil (HMdUrd) and 5 formyl-uracil (5-FordUrd). N- represents the bond to the DNA backbone.

Die allyl-standige Hydroxy-Gruppe des 5-Hydroxymethyl-uracils bleibt teilweise er-halten, wenn man mit Rhodium/Aluminiumoxid (5%) in Wasser hydriert1,2. Das Aus-maB der Hydrogenolyse nimmt durch Saure-Zusatz zu mit Platin(IV)-oxid in 50°/o-ig-Essigsaure erhalt man 95% d. Th. Thymin, das mit mehr Katalysator zu Dihydro-thymin weiterhydriert wird2 ... 

DNA is also susceptible to free radical attack during oxidative stress. The participation of GST isoenzymes in the detoxification and repair of the potentially mutagenic radical damage to DNA has been studied by Ketterer and his colleagues. Both thymine hydroperoxides and DNA peroxidized by ionizing radiation in the presence of oxygen have been shown to serve as substrates for rat GST (T3, T4). However, these workers reported that the specificity of rat GST isoenzymes toward the peroxidized DNA differs from that toward the free thymine hydroperoxide, 5-hydroxymethyl uracil. From their data, Ketterer et al. (K7, K9) propose that GST act in concert with DNA glycosylase to repair oxidized DNA. 

Methylisocytosine (LVIII, superacyl) has been reported to stimulate antibody production in rabbits to an extent greater than with a vaccine alone [354]. It also markedly reduced the development of pulmonary adenoma at 100 mg/kg per day for 10, 25 or 50 days s.c. or p.o. to mice, following a single i.p. injection of urethan. 5-Hydroxy-6-methylisocytosine had the same effect [19]. In tests on the effect of pyrimidines on reticuloendothelial functions in mice, the absorptive capacity of this system increased with 5-(hydroxymethyl)uracil or with 6-methylisocytosine. The effect was most pronounced when superimposed on cortisone inhibition [355]. When administered subcutaneously to mice, 6-methylisocytosine increased the inhibitory effect of thio-TEPA on the growth of Ehrlich tumours in mice. It is believed that this pyrimidine prevents the development of metastases [356]. 

The main oxidising agent of DNA is the hydroxyl radical (HO ), which oxidises the purine and pyrimidine bases and deoxyribosyl residues. The main oxidation products are 5-(hydroxymethyl)uracil (3-153) and S-hydroxyguanine (3-154), which is formed by reaction of guanine with singlet oxygen. In the presence of transition metals, the main compound that is attacked is adenine. The reaction product is adenine-N -oxide (3-155). 

The four bases mentioned account for most of those found in the DNA of higher forms of life. 5-methylcytosine forms the principal exception 25 per cent of the cytosine in the DNA of plants is in this form, but animals have much less, and bacteria have only 0--2 per cent (Vanyushin et al. 1968). Bacterial and viral DNAs sometimes contain other methylated bases, such as 6 -methyladenine, 2-methyladenine, or 5-hydroxymethyl-uracil. In some phages, all cytosine is replaced by 5-hydroxymethyl-cytosine, made by a virus-induced enzyme in the bacterial host (Cohen, 1963). 

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