[en] Most DNA damage by the hydroxyl radical is confined to the bases, and this base damage represents an important component of locally multiply demanded sites (LMOS). The yields of the major damaged bases have been determined by gas chromatography mass spectrometry. For our propose, it was necessary to convert a known fraction of these damaged bases to strand breaks and then assay these labile sites as the increase in strand break yield over the normally observed level. Three potential agents by which this strategy of conversion of base damage to strand break could be implemented were identified in the original application: 1, Sl nuclease; 2, piperidine; and 3, base damage specific enzymes

[en] Systems are described for examining the molecular mode of action of anoxic radiosensitizers with DNA--OH radicals. Pulse radiolysis showed that NPPN reacts with these radicals even in the presence of 0.5mM oxygen. Analysis of low molecular weight products liberated from DNA by irradiation showed that NPPN does not act in an oxygen-like way but that misonidazole does. Thus a molecular rationale exists for the use of combinations of radiosensitizers

[en] On the basis of literature data, a discussion is presented of the DNA damage which would be produced in a cellular environment and an attempt is made to place this damage in perspective as a potential hazard in food irradiation. The topics discussed are radiation damage mechanisms, OH reactions with DNA, base products, sugar products, and evaluation of damage from irradiated nucleic acids

[en] A comparison is made of the response to radiation in aqueous solution of single strand and double stranded DNA. Three types of experiment were performed: pulse radiolysis observations of the DNA-OH/sup ./ transient; measurement of neutral and alkali induced strand breaks; and assays of low molecular weight fragments of thymine released from the macromolecule. The results showed a marked effect of macromolecular structure on radiation response. A working hypothesis is developed that the nucleic acid bases are protected inside the double helix against the reactions of OH/sup ./ free radicals. Thus native DNA does not respond as a mixture of nanonucleotides. Thus care should be taken to use low radiation doses when studying radiation damage to DNA, large doses breaking down the macromolecular into a form which does not respond to radiation similarly to native DNA

[en] A solution of DNA was gamma-irradiated and treated with monophosphatase for studies on the amount of inorganic phosphate released as a function of time. Studies were also conducted on: effect of alkali on yield of monophosphate end groups; induction of DNA strand breaks by treatment with DNAase; initial G values for monophosphate termini; and effect of alkali on radioinduced DNA damage

[en] Gamma irradiation of DNA in dilute O₂-saturated aqueous solution releases free bases and damaged bases from the macromolecule. The yields of these products were measured after column chromatographic separation. For double stranded DNA the immediate yield of bases varies from G = 0.012 for cytosine to G = 0.033 for adenine. The yields of released bases increase with post-irradiation time (the majority of the increase occurs in the first 2 hrs.) to yields in the range of G = 0.07 +- 0.012. Yields of two released damaged thymine radiation products from γ-irradiated ³H thymine labelled DNA also increased with post-irradiation time. Strand breaks were measured in γ-irradiated single stranded DNA the initial yield G = 0.02 was low but increased with time to G = 0.07. No direct correlation between strand-break production and release of low molecular weight products is possible. The findings are discussed in terms of damage to DNA in vivo and its enzymatic repair

[en] Progress is reported on the following research projects: effects of high LET radiation on DNA in solution; and free radical formation in DNA and DNA components exposed to α-particles

[en] The integrity of DNA is essential for the well-being of a cell. Damage to this molecule, whether caused by reaction with chemical mutagens, by irradiation with ultraviolet (uv) light, or by ionizing radiation, has dire consequences. Thus, much effort has been expended in attempting to understand the effects of these agents on DNA. The intent of this review is to describe some of the chemical mechanisms whereby DNA is damaged by ionizing radiation. The major advances in understanding of molecular mechanisms have come from studies of simple model systems, and it is these systems that are considered in this review. To place the various model systems in perspective the general mechanisms of the conversion of energy to damage in a cellular system are discussed. Against this background, all the model systems discussed in the review are judged as to their validity to the in vivo situation. The major part of the review is devoted to data derived from aqueous systems. The goal of the discussion is to desribe at a molecular level radiation-induced reactions which would account for the DNA damage observed after in vivo irradiations: base damage and strand breaks. (200 references) (auth)

[en] Ionizing radiation deposits energy nonhomogeneously in the medium through which it passes. Mozumder and Magee (Radiat. Res. 28, 203-214(1966)) have classified the events as spurs, blobs, and short tracks. These are defined by size and amount of energy deposited. Thus the initial chemically reactive species are distributed in an inhomogeneous manner. In these volumes of high radical concentration, radical-radical reactions can occur which can only be scavenged by solutes at high concentration. Making the reasonable assumption that similar events occur intracellularly, the consequences of such events must be considered. In the case of DNA, several authors have shown that OH radicals diffuse only tens of angstroms prior to reaction. In the volume from which these radicals originate, DNA is necessarily at high concentration and consequently will interact with the radicals formed in the spur, etc. Such events are probably the source of radiation-production double-strand breaks in cellular DNA. However, the radicals cause other types of damage than strand breaks-potential strand breaks and base damage. An attempt is made to present the interrelation of multiply damaged sites - their constitution, the problems they present to cell repair mechanisms, and their possible relationship to cell survival

[en] Simple model systems were used to characterize the nature of radioinduced DNA strand breaks. Using DNA labeled with [³H] thymidine, it was shown that three monomeric thymine-derived products are released from DNA by irradiation. All three increase with time after irradiation. It was concluded that two post-irradiation time-dependent processes occur in macromolecular DNA: the yield of actual strand breaks increases by a factor of 2; and the chemical nature of the strand break terminus changes, i.e., the yield of monomeric bases continues to increase after the strand break yield has reached a maximum