Radiation-induced damage in DNA

Medical Research Council, Radiation Genome Stability Unit, Harwell, Didcot, Oxfordshire, 0X11 ORD, United Kingdom 

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Close DM (1999) Where are the sugar radicals in irradiated DNA Radiat Res 147 663-673 Close DM (2003) Model calculations of radiation induced damage in DNA constituents using density functional theory. In Leszczynski J (ed) Computational chemistry, reviews of current trends, Vol. 8. World Scentific, Singapore, pp 209-247... 

Model Calculations of Radiation Induced Damage in DNA Constituents Using Density Functional Theory (D. M. Close)... 

Model Calculations of Radiation Induced Damage in DNA Constituents 213... 

O Neill, P. (2001) Radiation-Induced Damage in DNA, in Radiation ChenUstry Present Status and Future Trends (eds C.D. Jonah and B.S.B. Rao), Elsevier Science, Amsterdam, p. 5. 

The interaction of UV radiation with nucleic acids is of great importance since it can lead to UV-induced damage in DNA with profound consequences, including photocarcinogenesis [1,2]. The nucleobases are the primary chromophores in DNA and RNA, and consequently, the photophysical and photochemical behavior of the nucleobases has been the focus of extensive theoretical and experimental work over the years [4, 6, 81, 82],... 

The greatest research effort on radiation sensitizers has focused on organic compounds however, platinum complexes conform to the hypotheses for radiation sensitizers since they are electron affinic and react preferentially with the hydrated electron in aqueous solution. Early studies of cisplatin in combination with radiation therapy suggested a synergistic effect in antitumor activity (50,51). Much of the initial data were obtained using cells in tissue culture (52), these data indicated that the potential of cisplatin to inhibit repair of radiation-induced damage to DNA could be an important contributor to the enhanced tumor cell killing seen in vivo by the combination of these two modes of treatment. 

Distel L, Distel B, Schussler H (2002) Formation of DNA double-strand breaks and DNA-protein crosslinks by irradiation of DNA in the presence of a protein. Radiat Phys Chem 65 141-129 Dizdaroglu M (1986) Chemical characterization of ionizing radiation-induced damage to DNA. Bio Techniques 4 536-546... 

Razskazovskiy Y, Debije MG, Bernhard AW (2003a) Strand breaks produced in X-irradiated crystalline DNA influence on base sequence. Radiat Res 159 663-669 Razskazovskiy Y, Debije MG, Elowerton SB, Williams LD, Bernhard AW (2003b) Strand breaks in X-irradiated crystalline DNA alternating CG oligomers. Radiat Res 160 334-339 Redpath JL, Zabilansky E (1979) Photoreactivation of ionizing-radiation-induced damage in E. coli. 

Sy D, Flouzat C, Eon S, Charlier M, Spotheim-Maurizot M (2001) Modelling radiation-induced damage in the lac operator-lac repressor complex. DNA damage 8-oxoguanine. Theor Chem Acc 106 137-145... 

A new book by von Sonntag, Free-Radical Induced DNA Damage and Its Repair has just appeared [7], This new book provides thorough updates on what is currently known about the free radical chemistry of nucleic acids. This book also contains a section on irradiation in the solid-state. Since there is no need to repeat what has already been so adequately covered, the present work will focus on the experimental techniques used to obtain the detailed structure of the primary radiation induced defects in DNA model systems, and to consider the subsequent transformations these primary radical undergo. 

This review has spanned many years of work devoted to the attempts to understand the effects of radiation damage to DNA. The emphasis has been on the use of EPR/ENDOR spectroscopy to reveal the structures of the primary radiation induced products in DNA. ENDOR was invented before 1960, but it took quite some time before this technique was used to study problems in radiation biology. The basic reason is that complex equipment had to be designed and tested that permits the irradiation and examination of small single crystals at helium temperatures. The apparatus was only completed around 1975 by Bernhard and co-workers in Rochester, and by Huttermann and co-workers in Regensburg. 

MS-MS measurements performed recently in our laboratory have shown that the yield of radiation-induced formation of (5 R)-cydodAdo (44a) in cellular DNA is at best around 0.2 lesions/109 normal nucleotides/Gy. This is in agreement with the fact that the shielding effect exerted by cellular constituents on the extent of radiation-induced damage to DNA bases and sugar is about three orders of magnitude with respect to naked DNA [12]. 

It should be noted that DNA can hardly be totally freed from water. Commonly, a certain number of water molecules (about 8-12 per nucleotide) are tightly associated with the different parts of the macromolecule, forming a primary solvation shell. However, when the water molecules are ionized, hole transfer to the DNA molecules can occur and electrons ejected from the water molecules can be scavenged by DNA molecules (Scheme 5.17). In fact, the existence of a primary solvation shell can cause an increase in the radiation-induced damage to DNA by about 50% [90]. 

In single crystals of deoxyadenosine [45], the site of oxidation seems to be the deoxyribose moiety. This brings up an interesting point. In studies of the radiation-induced defects in nucleosides and nucleotides, one often sees evidence of damage to the ribose or deoxyribose moiety. These radicals have not been discussed here because much less is known about sugar-centered radicals in irradiated DNA. 

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