Free radicals damage to DNA

Long term Free radical damage to DNA/cell membranes... 

Kuraoka, L, Robins, P., Masutani, C., Hanaoka, F., Gasparutto, D., Cadet, J., Wood, R. D., and Lindahl, T. (2001). Oxygen free radical damage to DNA. Translesion synthesis by human DNA polymerase rj and resistance to exonuclease action at cyclopurine deoxynucleoside residues. /. Biol. Chem. 276, 49283-49288. 

Dizdaroglu, M., Chemistry and free radical damage to DNA and nucleoproteins, in DNA and Free Radicals, HalliweU, B. and Aruoma, O.I., Eds., Ellis Harwood, Chichester, United Kingdom, 1993, pp. 19-39. 

The -N02 radical (and also the C03 radical) are of some biological interest (Augusto et al. 2002) because they play some role in the reactions of peroxyni-trite (Chap. 2.4). For example, "N02 oxidizes tyrosine to nitrotyrosine (Prutz et al. 1985b), and the latter has been considered a promoter of free-radical damage in DNA model systems (Prutz 1986). In this context, it may be of interest that CCV reacts with a self-complementary ODN (k = 1.9 x 107 dm3 mol-1 s 1) exclusively at G (by ET) (Chap. 11.2). 

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. 

Additionally, energy deficits lead to ionic imbalance, and excito-toxic glutamate efflux and buUd up of intracellular calcium. Downstream pathways ultimately include direct free radical damage to membrane lipids, cellular proteins, and DNA, as well as calcium-activated proteases, plus caspase cascades that dismantle a wide range of homeostatic, reparative, and cytoskeletal proteins (courtesy of DaLkara et al. 2003)... 

Travascio, P., Witting, P. K., Mauk, A. G., Sen, D. (2001). The peroxidase activity of a hemin-DNA oligonucleotide complex free radical damage to specific guanine bases of the DNA. J Am Chem Soc 123, 1337-1348. 

Fischer T.W., Slominski A., Zmijewski M.A., Reiter R.J., and Pans R. 2008. Melatonins as a major skin protectant From free radical scavenging to DNA damage repair. Experimental Dermatology 17 713-730. 

SASPs comprise about 10-20% of the protein in the dormant spore, exist in two forms alfi and y) d are degraded during germination. They are essential for expression of spore resistance to ultraviolet radiation and also appear to be involved in resistance to some biocides, e.g. hydrogen peroxide. Spores (a /3 ) deficient in a//3-type SASPs are much more peroxide-sensitive than are wild-type (normal) spores. It has been proposed that in wild-type spores DNA is saturated with a/j3-type SASPs and is thus protected from free radical damage. 

As mentioned earlier, cancerous mutations can occur as a result of oxidative damage to DNA caused by free radicals generated as a damaging side-effect... 

Dizdaroglu, M. (1991). Chemical determination of free radical-induced damage to DNA. Free Rad. Biol. Med. 10, 225-230. 

Dilly O, loemJ B, Vos A, Munch JC (2004) Bacterial diversity in agricultural soils during litter decomposition. Appl Environ Microbiol 70 468-474 Dizdaroglu M (1991) Chemical determination of free radical-induced damage to DNA. Free Radical Biol Med 10 225-242 Eaton RW, Ribbons DW (1982) Metabolism of dimethylphthalate by Micrococcus sp. strain 12B. JBacteriol 151 465-467... 

It is the damage to DNA in the epithelial cells of the skin that is usually considered to be the cause of the development of melanoma due to excessive exposure to sunlight (Chapter 21). However, an alternative or additional mechanism could be the damage to polyunsaturated fatty acids in membrane phospholipid in the epithelial cells. This could be due, as in the case of DNA damage, to the local production of free radicals (Appendix 9.6). The damaged polyunsaturated fatty acids (e.g. peroxidised or hydroperoxide fatty acids) will disrupt the membrane which might facilitate the binding of key proteins of proliferation to these membranes or result in the production of abnormal eicosanoids either of which could facilitate inappropriate proliferation. 

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