DNA reaction

SCHEME 7.13 Probing the DNA reaction products of the ene-imine and quinone methide. 

Fig. 3.13. A simplified version of a genetic construct which requires not only a reading frame to generate the m-RNA and then the protein but requires a binding region for the polymerase machinery and an instruction region for the binding of a transcription factor, both of which must be bound in appropriate form before reading can occur. The form of the transcription factor which may interact by feedback with an element, M, can be adjusted (by [M]) to stop reading. The whole is necessary for cell operations not just for that of DNA reactions.

In addition to influencing hydrocarbon metabolite-DNA reactions, the physical binding properties of hydrocarbon metabolites covalently bound to DNA may also be important to carcinogenic activity. The covalent binding of ultimate carcinogens derived from BP and DMBA to DNA produces adducts with tt binding properties similar to those of naturally occurring nucleotides. These adducts... 

In the presence of DNA reactions (17) and (18) that generate the excited complex directly or indirectly via reaction (19), become much slower or do not take place, and therefore the ECL disappears. This is due to the fact that the Ru(II) and Ru(III) complexes, physically bound to DNA, are protected by the negatively charged phosphate backbone from the reduction by C02. Thus the ECL titration of the metal complex in the presence of DNA has allowed the determination of the equilibrium constant and binding-site size for association of Ru(phen)3 to DNA [82]. 

S12. Swerdlow, H., Jones, B. J., etal., Fully automated DNA reaction and analysis in a fluidic capillary instrument. Anal. Chem. 69(5), 848-855 (1997). 

Scholes, G. Willson, R.L. Ebert, M. Pulse radiolysis of aqueous solutions of deoxyribonu-cleotides and of DNA reaction with hydroxyl radicals. Chem. Commun. 1969, 17. 

Transfer of radiation-induced electrons and holes (H20 ) from the hydration layer of DNA has been of considerable recent interest. Results from ESR experiments at low temperatures suggest that ionization of hydration water (reaction 4) results in hole transfer to the DNA (reaction 5) [4, 24-28]. Since the proton transfer reaction (reaction 6) to form the hydroxyl radical likely occurs on the timescale of a few molecular vibrations [29], it is competitive with and limits hole transfer to DNA [27]. 

The concentration of the unknown DNA solution can be calculated by a simple comparison of the fluorescence intensity obtained from the standard DNA reaction mixture (Fstd) and the fluorescence of the unknown DNA mixture (Equation E13.2). 

The same type of reaction, starting from the radical at C(4 ), leads to strand breakage in DNA [reaction (45) (Dizdaroglu et al. 1975a) Chap. 12.4],... 

ScholesG, Willson RL, Ebert M (1969) Pulse radiolysis of agueous solutions of deoxyribonudeotides and of DNA reaction with hydroxy-radicals. Chem Commun 17-18 Schuchmann MN, von Sonntag C (1982) Flydroxyl radical induced oxidation of diethyl ether in oxygenated aqueous solution. A product and pulse radiolysis study. J PhysChem 86 1995-2000 Shragge PC, Michaels FIB, Flunt JW (1971) Factors affecting the rate of hydrated electron attack on polynucleotides. Radiat Res 47 598-611... 

The direct effect gives rise to a DNA radical cation (DNA,+) and an electron in addition to electronically excited DNA (DNA ) [reaction (1)]. The DNA,+ may undergo rapid hole transfer to G (GG GGG) sites (see Sect. 12.10) in competition with other reactions. 

Under hypoxic conditions, cellular enzymes reduce the benzotriazine di-N-oxide [(reaction (68) P450 reductase Cahill and White 1990 and NADPH may be involved Walton et al. 1992 Wang et al. 1993]. Upon microsomal reduction of tirapazamine the radical formed in reaction (68) has been identified by EPR (Lloyd et al. 1991). Using the pulse radiolysis technique, it has been shown that this radical has a pKd of 6 (Laderoute et al. 1988), and it is the protonated form that undergoes the DNA damaging reaction (Wardman et al. 2003). The rate constants of the bimolecular decay of the radical [reaction (70)] has been found to be 2.7 x 107 dm3 mol-1 s 1. The reaction with its anion is somewhat faster (8.0 x 108 dm3 mol-1 s 1), while the deprotonated radicals do not react with one another at an appreciable rate. From another set of pulse radiolysis data, a first-order process has been extracted (k = 112 s 1) that has been attributed to the water elimination reaction (72), and the tirapazamine action on DNA [reaction (74)] has been considered to be due to the resulting radical (Anderson et al. 2003). 

Tang, T., Ocvirk, G., Harrison, D.J., Iso-thermal DNA reactions and assays in microfabricated capillary electrophoresis systems. Transducers, 1997, Jun 16-19, 523-526. 

These analyses show major differences in the DNA reaction products formed by DMBA and by BP, a weaker but much more extensively studied polycyclic aromatic hydrocarbon carcinogen (35). 

Syn dihydrodiol epoxide adducts formed in mouse skin treated with benzo[ ]pyrene constitute only about 12% of the total binding (36) and dihydrodiol epoxide deoxyadenosine adducts account for even less (2 to 3%) of the total (37,38). DMBA is approximately 20 times more potent a carcinogen than BP and this difference cannot be explained by the 2- to 4-fold difference in overall binding to DNA by these two carcinogens in mouse skin (35). Thus, these more subtle differences in DNA reaction products, i.e. the difference in reaction of syn-stereoisomer with DNA or in the modification of deoxyadenosine residues, might account for the greater tumor-initiating potential of DMBA. 

Newbold, R.F., C.B. Wigley, M.H. Thompson, and P. Brookes. Cell-mediated mutagenesis in cultured Chinese hamster cells by carcinogenic polycyclic hydrocarbons Nature and extent of the associated hydrocarbon-DNA reaction. Mutat. Res. 43 101-116,... 

Detailed Protocol for Gel Analysis of Randomly Amplified Polymorphic DNA Reactions... 

Methylazoxymethanol (Euphorbiaceae) [seed] From deglvcosylation of Cycasin DNA reaction breakage... 

Dipple, A., Khan, Q. A., Page, J. E., Ponten, I. Szeliga, J. (1999). DNA reactions, mutagenic action and stealth properties of polycyclic aromatic... 

While e does not react with the sugar-phosphate moiety, presolvated electrons that retain some excess energy may also undergo dissociative attachment to the phosphate group of DNA [reactions... 

Tirapazamine is inactivated by two-electron reduction steps catalyzed by quinone reductase, yielding first the mono-N-oxide (reaction a and compound 18). In contrast, it is activated to a cytotoxic nitroxide (16) by a one-electron reduction catalyzed by NADPH-cytochrome P450 reductase (reaction b). This delocalized radical loses one molecule of water to yield a reactive radical (reaction c and compound 17). Radical 17 can then abstract one hydrogen radical from DNA (reaction d and compound 18), leading to DNA breaks and cytotoxicity. In summary, both inactivation and activation involve reduction reactions, but cytotoxicity will depend on the relative levels of quinone reductase and CYP reductase in hypoxic cells. 

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