Strand scission of DNA

HydroxymethylquinoxalLne (and a corresponding ester, methyl 2-quinoxaline-carboxylate) have been found to induce significant single-strand scission of DNA by additive-free irradiation at 365... 

On the other hand, if the hole flow in DNA could be artificially controlled to deposit at the desired site in DNA, it may enable site-selective oxidation and strand scission of DNA, which is desirable from a therapeutical standpoint. Furthermore, understanding DNA-mediated hole transfer is expected to lead to an additional application in the development of biosensors and bioelectronic devices [9]. Therefore, the regulation of the transfer rate and direction of the hole generated in DNA is of interest from the perspective of using DNA as a building block for electronic devices. 

Giloni L, Takeshita M, Johnson F, Iden C, Grollman AP (1981) Bleomycin induced strand-scission of DNA. Mechanism of deoxyribose cleavage. J Biol Chem 256(16) 8608-8615 Gniazdowski M, Czyz M (1999) Transcription factors as targets of anticancer drugs. Acta Biochim Pol 46(2) 255-262... 

Cytochrome P-450 reductase (present in cell nuclear membranes) catalyzes reduction of the anthracyclines to semiquinone free radicals. These in turn reduce molecular 02, producing superoxide ions and hydrogen peroxide that mediate single strand scission of DNA (Figure 38.10). Tissues with ample superoxide dismutase (SOD) or glutathione peroxidase activity are protected.6 Tumors and the heart are generally low in SOD. In addition, cardiac tissue lacks catalase and thus cannot dispose of hydrogen peroxide. This may explain the cardiotoxicity of anthracyclines. 

Single- and double-strand scission of DNA, together with hydroxylation of constituent bases, are changes characteristic of oxygen-radical attack on DNA. An important mechanism is site-specific hydroxyl-radical generation, catalysed... 

Giloni, L., Takeshita, M., Johnson, F., Iden, C. andGtollman, A.P. (1981). Bleomycin-induced strand scission of DNA mechanism of deoxyribose cleavage. J. Biol. Chem. 256, 8608-8615. 

The in vitro activity (strand scission of DNA) was determined asdesoibed in [236]. The activity of each compound is expressed as that relative to the activity of bleomycin Ba (100%). 

Structure—activity studies show a great variation, both in strand scission of DNA and antibacterial activity, with change in the chemical structure. The role... 

On the other hand, quercetin in common with (-)-epicatechin (Chrisey et al. 1988) and 4 -(9-acridinylamino)methanesulphon-m-anisidine (Wong et al. 1984), can reduce oxygen to produce superoxide without the involvement of a thiol or other reducing agent (Fazal et al. 1990). The hydroxyl radical can be produced from quercetin and Cu(II) by alternative pathways. The strand scission of DNA was shown to occur under conditions in... 

Lown, j. W., and S.-K. Sim Studies Related to Antitumor Antibiotics. Part VII. Synthesis of Streptonigrin Analogs and Their Single Strand Scission of DNA. Canad. J. Chem. 54, 2563 (1976). 

It has been recently shown that the selective alkylation and strand scission of deoxytetranucleotide d(GTAG)-27 chosen as DNA model, results from the formation of covalent adducts 28 and 29 on the N-7 of guanine and N-3 of adenine with opening of the cyclopropane ring, respectively. Thermal treatment of 28 (90 °G, 5 min) afforded the d(deoxyribose-TAG) 30 with liberation of N-7 alkyl-guanine 31, while treatment of 29 provided the d(GT-deoxyribose-G) 32 and the N-3 alkyladenine 33 [27]. The stabilities of adducts 28 and 29 were tj/2 = 31 h and 3.2 h, respectively therefore, the cleavage reaction of adduct 29 proceeds much faster than that of 28, Eq. (11) [27]. 

The radical-induced dephosphorylation of sugar phosphates (see Sect. HI,3) and the scission of DNA strands (see Sect. Ill,6) are mainly due to these reactions, at least in the absence of molecular oxygen. 

Rahman A, Shahabuddin, Hadi SM, Parish JH, Ainley K (1989) Strand scission in DNA induced by quercetin and Cu(Il) role of Cu(l) and oxygen free radicals. Carcinogenesis 10 1833-1839 Rahman 1, Marwick J, Kirkham P (2004) Redox moxlulation of chromatin remodeUng impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Bioxthem Pharmacol... 

Guidarelli A, Tommasini 1, Fiorani M et al. Essential role of the mitochondrial respiratory chain in peroxynitrite-induced strand scission of genomic DNA. lUBMB Life 2000 30(3) 193-201. 

Guidarelli A, Fiorani M, Cantoni O. Calcium-dependent mitochondrial formation of species promoting strand scission of genomic DNA in U937 cells exposed to tert-butyUiydropetoxide The role of arachidonic add. Free Radic Res 2000 33(3) 477-487. 

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