DNA oxidizing agents

Cl oxidation has been observed with many other DNA oxidizing agents such as y-radiolysis, neocarzinostatin, Mn-TMPyP (4,5,7), copper complexes of benzosulfonamides (40), Cu-kanamycin (41), or for copper complexed to guanine of DNA (42), but it was not associated to direct strand-cleavage events except for metal complexes like Cu(3-Clip-Phen) (43), or Ru(terpyridine)(bipyridine) complexes (44). 

Abstraction of the Cl -hydrogen atom in duplex DNA by diffusible species (eg HO ) is Hmited by its position in the minor groove (Fig. lA), despite the relatively modest Cl -H BDE (Table 1). The solvent inaccessibility of the CT-hydrogen is overcome by DNA oxidizing agents that bind in the minor groove. For instance, the antitumor agent neocarzinostatin... 

The development of nontransmittable chronic illnesses is associated with the presence of oxidative agents in the body. These agents are found in air, water, or food or can be produced in the body s cells. Their high content in body cells causes an imbalance that results in oxidative stress damaging proteins, DNA, and others. As a result of this deterioration, an increase in the risk of nontransmittable chronic illnesses has been noted. In order to prevent or decrease oxidative stress, the consumption of foods rich in antioxidants, such as fruits and vegetables, is recommended (van Dokkum and others 2008 Liu 2003). 

While the successful DNA cleavage with copper(II)acetate establishes the mediacy of a similar activation mechanism with kinamycins, as shown before with 9-diazofluorenes, their mode of action may or may not involve the use of an oxidizing agent under physiological conditions. An important cor-... 

The kinetics and mechanisms of the oxidation of DNA, nucleic acid sugars, and nucleotides by [Ru(0)(tpy)(bpy)] and its derivatives have been reported. " The Ru =0 species is an efficient DNA cleavage agent it cleaves DNA by sugar oxidation at the 1 position, which is indicated by the termini formed with and without piperidine treatment and by the production of free bases and 5-methylene-2(5//)-furanone. Kinetic studies show that the I -C— activation is rate determining and a hydride transfer mechanism is proposed. The Ru =0 species also oxidizes guanine bases via an 0x0 transfer mechanism to produce piperidine-labile cleavages. 

Interestingly, it was shown that 8-oxodGuo 46, an ubiquitous exposure marker of DNA exposed to most oxidizing agents , is a much better substrate than dGuo 36 to further oxidation by O2 and one-electron oxidants. 

Such changes can occur spontaneously or from exposure to chemicals. Cytidine can be deaminated to uridine (Fig. 6.42) and adenine to hypoxanthine (Fig. 6.43) by exposure of DNA to the oxidizing agent nitrous acid. 

UV and ionizing radiation affect DNA and RNA. Strong oxidizing agents that penetrate the cell wall also alter DNA and RNA. Ultrasonic energy vibrates the cells until they disintegrate. 

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