No description available.

In this study the direct effect of ionising radiation on DNA plus additives has been studied using both ESR spectroscopy and plasmid DMA (for strand break analysis). The primary radicals were identified as the thymine radical-anion, T', and guanine radical-cation, G'*'. Under normal conditions these were formed in approximately equal yields as defined by careful computer simulations. Certain additives such as oxygen, nitroimidazoles, silver ions and the rest of the nuclear complement (i.e. RNA and histone proteins) , were added to study their effects on the relative yields of T" and G". In all cases, they were shown to capture electrons in competition with T" and have little or no effect on the yield of G"*". In the case of oxygen and nitroimidazoles the effect of reducing the yield of T" radicals was looked at using strand break analyses. Essentially this was found to protect the DNA. Since both single and double strand breaks were found at significant levels when G+ and T~ were the only detectable initial radicals, one must conclude that these radicals are responsible for strand breaks. Fran the relatively high number of double strand breaks found, we deduce that G'*' and T" centres must be close togetlier (in a range of ca. 10-50 A), and that both may give rise to strand breaks, by as yet undefined pathways. In a separate study (Chapter 4), the reaction between superoxide ions, O2"/ and dimethyl formamide has been investigated by ESR spectroscopy. Strong evidence in favour of addition of O2" at the C=0 group to give a relatively stable peroxy radical intermediate has been obtained. This has implications for the mechanism of action of O2" formed both as a result of radiation damage and by other means. Appendix I describes a study of various simple aldehyde and ketone radical-cations, using ESR spectroscopy. Interpretations of these spectra are given, together with structural implications. Appendix II is a paper on work carried out on the ESR spectra of hydroxyl radicals in aqueous glasses. This work was done in collaboration with H. Riederer and J. Hiittermann.

The major target of ionising radiation has been determined as cellular DNA. Damage to DNA, as detected at 77K under conditions of direct damage by ESR, is localised on the bases thymine and guanine. This damage leads to single and double strand breaks, precursors of cell death and mutagenesis. In an attempt to intercept the damage at the bases, before formation of strand breaks, the use of polycations as potential drug delivery systems to DNA has been examined. Magnetic resonance techniques have been used to establish that polyamines used are present almost completely as polyammonium cations at pH 7 and to probe the interactions of a number of polycations with DNA. Sodium-NMR was used to investigate the affinity of polyamines, poly- aminothiols and transition-metal complexes for DNA, via sodium ion displacement from the DNA region. It was found that small metal complexes displace a greater number of sodium ions than polyamines of similar charge. Application of the counterion condensation theory led to a model of the counterions existing within a cylinder around the DNA of approximate radius 20A. The mode of interaction of polyammonium cations was studied using proton magnetic resonance. Linewidths, related to the transverse relaxation rate, give information on the motion of compounds close to DNA. Comparison of linewidths in the presence and absence of DNA revealed no significant broadening. This was interpreted as indicative of a loose, electrostatic interaction, not significantly hindering motion of the cations close to DNA, suggesting rapid motion of polyammonium ions along the DNA. The radioprotection of DNA by various transition-metal complexes was studied using ESR. Certain compounds exhibited protection via electron transfer, resulting in a decreased radical yield.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.