DNA oxidative damage

H. Bernstein, C. M. Payne, C. Bernstein, J. Schneider, S. E. Beard and C. L. Crowley, Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate, Toxicol. Lett., 1999, 108(1), 37. 

Culmsee C, Bondada S, Mattson MP. 2001. Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity. Mol Brain Res 87 ... 

Tirapazamine (21, Scheme 9) is a benzotriazine di-iV-oxide bioreductive anticancer prodrug. Tirapazamine is activated to a DNA-damaging oxidizing radical by cytochrome P450 reductase and other one-electron reductases in the absence of oxygen.38,39 Tirapazamine has been demonstrated to be effective in killing... 

The mitochondria have emerged as a central component of the intrinsic apoptotic signaling pathways and are now known to control apoptosis via the release of apopto-genic proteins (Fig.15.8). The apoptotic signals that are channeled through the mitochondrial pathway of apoptosis include various stresses like DNA damage, oxidative stress, UV radiation, protein kinase inhibition, and growth factor deprivation. 

Casadevall, M., da Cruz Fresco, P., and Kortenkamp, A., Chromium(VI)-mediated DNA damage oxidative pathways resulting in the formation of DNA breaks and abasic sites, Chem. Biol. Interact, 123, 117-132, 1999. 

ROS and RON can react with the DNA molecule and induce purine or p)u imidine base or sugar lesions, nitration and deaminations of purines, and DNA-DNA or DNA-protein cross-links (Dizdaroglu et al., 2002). These processes lead to mutations and impaired transcriptional and posttranscriptional processes and compromise protein synthesis (Colurso et al., 2003). In addition, DNA damage, oxidative phosphorylation, and altered cell metabolism may lead to apoptosis and promote neuronal death (Fishel et al., 2007 Becker and Bonni, 2004). ROS and RNS can also attack amino acids, leading to the formation of carbonyl derivatives (Stadtman and Levine, 2003). Oxidation of protein also leads to protein fragmentation and protein cross-linking. In addition, peroxynitrite and a hydroxyl radical can react with tyrosine and form other indexes of protein oxidation,... 

Hamasaki et al. (1992) reported that monobutyltin oxide, monobutyltin trichloride, and dibutyltin dichloride showed high SOS-inducing potency in the SOS chromotest with iiic/rerrc/rra co/r PQ 37. Dibutyltin dichloride and dimethyltin dichloride were also recognized as producing DNA damage by the rec-assay in Bacillus subtilis H 17 Rec and M45 Rec. Li et al. 

Lodovici M, Casalini C, Briani C, et al. 1997. Oxidative liver DNA damage in rats treated with pesticide mixtures. Toxicology 117 55-60. 

Hauser, R., Meeker, J.D., and Singh, N.R et al. (2007). DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human Reproduction 22, 688-695. 

Wellejus, A., Dalgaard, M., and Loft, S. (2002). Oxidative DNA damage in male Wistar rats exposed to di- -bntyl phthalate. Journal of Toxicology and Environmental Health—Part A 65, 813-824. 

DNA Membrane Oxidative Protein damage damage damage damage... 

PILLION L, COLLINS A and SOUTHON s (1998) Beta-carotene enhances the recovery of lymphocytes from oxidative DNA damage. Acta Biochim Pol. 45(1) 183-90. 

WEI H, CAO Q AND RAHN R o (1996) Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. Carcinogenesis. 17 (1) 73-7. 

REHMAN A, BOURNE L c, HALLiwELL B and RicE-EVANS c A (1999) Tomato Consumption modnlates oxidative DNA damage in hiunans , Biochem Biophys Res Commun, 262, 828-31. 

Chen, L. et al.. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention, J. Natl. Cancer Inst., 93, 1872, 2001. 

Ames, B.N. (1989). Endogenous oxidative DNA damage, aging and cancer. Free Rad. Res. Commun. 7, 121-127. 

Bashir, S., Harris, G., Denman, A.M., Blake, D.R. and Win-yard, P.G. (1993). Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune disease. Ann. Rheum. Dis. 52, 659-666. 

Subjecting cells to oxidative stress can result in severe metabolic dysfunctions, including peroxidation of membrane lipids, depletion of nicotinamide nucleotides, rises in intracellular free Ca ions, cytoskeletal disruption and DNA damage. The latter is often measured as formation of single-strand breaks, double-strand breaks or chromosomal aberrations. Indeed, DNA damage has been almost invariably observed in a wide range of mammalian cell types exposed to oxidative stress in a number... 

Table 13.2 Methods used to subject cells to oxidative stress that has produced increased intracellular DNA damage (see Halil well and Aruoma, 1991)...

Possible Mechanisms of DNA Damage Induced by Oxidative Stress... 

A second explanation of the ability of oxidative stress to cause DNA damage is that the stress tri ers a series of metabolic events within the cell that lead to activation of nuclease enzymes, which cleave the DNA backbone. Oxidative stress causes rises in intracellular free Ca, which can fiagment DNA by activating Ca -dependent endonucleases (Orrenius etal., 1989 Farber, 1990 Ueda and Shah, 1992) in a mechanism with some of the features of apoptosis (see Wyllie, 1980). An example of apoptosis is the killing of immature thymocytes by glucocorticoid hormones, which activate a cell-destructive process that apparently involves DNA fragmentation by a Ca -dependent nuclease. 

These two mechanisms (DNA damage by OH or by activation of nucleases) are not mutually exclusive, i.e. they could both take place (Fig. 13.1). Indeed, there is evidence consistent with the existence of both mechanisms. Their relative importance may depend on the cell type used and on how the oxidative stress is imposed (Halliwell and Aruoma, 1991). For example, chelating agents that bind iron ions into chelates unable to generate OH (such as desferrioxamine. 

Figure 13.1 Hypotheses to explain DNA damage resulting from exposing cells to oxidative stress.

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