For over 100 years, cancer radiation therapy has provided patients with increased survival rates. Despite this success, radiation exposure poses a threat to the progeny of exposed parents. It causes transgenerational genome instability that is linked to transgenerational carcinogenesis. The exact mechanisms in which this instability occurs have yet to be discovered. Current evidence points to their epigenetic nature, specifically changes in DNA methylation. Using mouse and rat models, this thesis investigated the transgenerational effects of radiation in the offspring from parents who received whole body or localized exposure to ionizing radiation (IR). Both types of exposure resulted in significant global DNA hypomethylation in the somatic tissues of the progeny. These changes were paralleled by the significantly decreased levels of methyltransferases and methyl-CpG-binding protein. In summary, our results suggest that both localized and whole body parental exposures to IR result in transgenerational epigenetic instability within the unexposed offspring. / vii, 106 leaves : ill. ; 29 cm.

Bystander effects are traditionally known as a phenomenon whereby unexposed cells exhibit the molecular symptoms of stress exposure when adjacent or nearby cells are traversed by ionizing radiation. However, the realm of bystander effects can be expanded to include any systemic changes to cellular homeostasis in response to a number of biotic or abiotic stresses, in any molecular system. This thesis encompasses three independent experiments looking at bystander and bystander-like responses in both plant and animal models. In plants, an investigation into the regulation of small RNAs has given us some insights into the regulation of the plant hormone auxin in both stress-treated and systemic (bystander) leaves. Another plant model shows that a bystander-like plant-plant signal can be induced upon ionizing radiation to increase the genome instability of neighbouring unexposed (bystander) plants. In animals, it is shown that the microRNAome is largely affected in the bystander cells in a three-dimensional human tissue model. In silico and bioinfomatic analysis of this data provide us with clues as to the nature of bystander signalling in this human ‘in vivo’ model. / xiv, 141 p. : ill. ; 29 cm.

No description available.

No description available.

Auger electrons have the potential for therapy mainly because of their short range and high level of toxicity. Biological effects of these electrons are critically dependent on the cellular and subcellular localization of their emitters. In this study 123I was used due to its relatively short half-life (13.2 h) and ideal y-ray energy (Ey=I59 keV). The short half-life is advantageous since it allows significant accumulation of disintegrations at normal physiological conditions without the need to freeze cells as required when long lived isotopes such as 1251 (T1/2=60.1 days) are used. The main objective of this study was to synthesize an organic compound that would deliver the radioactive 1231 into cellular DNA and to quantify the resulting damage from micronucleation. The higher degree of damage obtained in cell samples treated with 4-[123I]iodoantipyrine than with [123I]Nal is an indication of Auger electron effect. Also, micronuclei counts showed that 4-[123I]iodoantipyrine and [123I]Nal were prepared in a suitable manner and did not interfere with cellular kinetics. RBE values of 1.8 and 1.9 were obtained for CHO-Kl clone # 7 and # 16 cells, respectively, indicating lack of differential response for the two clones. When the current data is collectively analysed with that of other investigators using the same radiolabeled compounds, a reduction in Auger electron RBE is noticeable with radiosensitivity. This is consistent with the high-LET nature of Auger electrons. The extremely radiosensitive CHO-XRS 1 failed to give a dose-response as most cells underwent apoptosis. The significant radioprotection of CHO-K1 cells irradiated, in the presence of a chemical protector MEA, with 4-[ 123I]iodoantipyrine than with [123I]Nal showed that the mode by which Auger electrons cause damage is not the same as that of a-particles. Further studies involving the use of carriers that would specifically deliver radionuclides to nuclear DNA may be useful in understanding the mechanisms underlying the cellular responses to Auger electron exposure. / Thesis (M.Sc. (ARST) North-West University, Mafikeng Campus, 2005

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 188-196).

Thesis--Oulun yliopisto, 1992. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Following reports that limited gene transfer may be facilitated by making crosses with irradiated pollen, a debate has arisen as to the cause of the observed results. If maternal trends that occurred in the second generation (the M2) were largely due to the persistence of radiation induced damage, then pollen irradiation would be of little value to plant breeders. But if much of the paternal genome had been eliminated, the method could offer breeders a cheap and simple means of transferring just a few characters from one plant genome to another. By carrying out reciprocal irradiated and control crosses, it was shown in this study with barley that mutational damage is not widespread in the M2. However, consistent trends away from the F2 towards the maternal expression were not observed either. When instead the female gamete was irradiated, moderate shifts to the paternal expression did occur. As trends were for increased vigour, mutational damage is unlikely to have been the cause of these observations. By contrast, when irradiated pollen crosses were made between three varieties of potato, the M1 and M2 were consistently lower scoring than the controls. It is suggested that the results may have been different in the two species because polyploids such as the potato may be better able to tolerate radiation damage than diploids such as barley. Gamete irradiation may, therefore, be of little value in polyploid crops. It is recommended that, at least in diploid species, ovule irradiation should be further investigated because not only may it be more effective than its male equivalent, but it may also be easier to perform. Both techniques may be useful in breaking down linkages resistant to conventional crossing.

No description available.

The Pectoralis major and Pectoralis minor muscles of chicken were given substerilizing doses of ɤ-irradiation at varying times post-slaughter and the pH, shear force, fragmentation, and color were evaluated. pH measurements in an iodoacetate slurry showed that doses up to 300,000 rads administered at ⅕ or 5 hours post-mortem had no effect on either rate of pH fall or final pH. Irradiation at 2, 5t or 12 hours did not change the final pH taken at 48 hours post-mortem. Excised P. major muscles cooked by boiling between aluminium plates required more shear force at the posterior portion than at the anterior. Irradiation dose levels from 30,000 to 300,000 rads on P. major increased shear resistance over unirradiated muscles. The earlier the time of application (2, 5 and 12 hours post-slaughter) the greater the increase in toughness when measured at 60 hours post-slaughter. The 300,000 rad dose at 12 hours, given after attainment of maximum inextensibility and relaxation of isometric tension, still produced a significant loss in tenderness. The irradiation generally reduced the degree of myofibrillar fragmentation after a standardized blending treatment, although the decrease was not always significant. Pasteurizing irradiation produced a pink color in raw muscle stored aerobically for 55 hours that increased with dose. Peaks typical of an oxymyoglobin-like compound emerged and the dominant wavelength was shifted toward longer wavelengths by 4 nm. After cooking there was no visible color difference between irradiated and control muscles. Correlations between these parameters on control muscles indicated that the pH decline was positively correlated to shear force, although not of high value. The fragmentation ratios were not significantly correlated with shear force. / Land and Food Systems, Faculty of / Graduate