No description available.

No description available.

No description available.

Bibliography: leaves 267-287.

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.

Ionizing radiation (IR), along with being an important diagnostic and treatment modality, is a potent tumor-causing agent, and the risk of secondary radiation treatment-related cancers is a growing clinical problem. Now some studies propose to link secondary radiation-induced cancers to an enigmatic phenomenon of bystander effects, whereby the exposed cells send signal damage and distress to their naïve neighbors and result in genome destabilization and carcinogenesis. Yet, no data existed on the bystander effects in an organ other than an exposed one. With this in mind, we focused on the analysis of existence and mechanisms of radiation-induced bystander effects in vivo. We have found that bystander effects occur in vivo in distant skin and spleen following half-body or cranial irradiation. These bystander effects resulted in elevated DNA damage, profound dysregulation of epigenetic machinery, and pronounced alterations in apoptosis, proliferation and gene expression. Bystander effects also exhibited persistency and sex specificity. The results obtained while using the animal model systems can potentially be extrapolated to different animals and humans. / xiii, 208 leaves : ill. ; 29 cm.

Bibliography: leaves 267-287 / xviii, 287, [ca. 40] leaves, [10] leaves of plates : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1985

The ICRP recommends a radiation weighting factor of one for all low-LET radiation. However, many experimental studies find inconsistencies between low-LET RBE and the ICRP's current radiation weighting factor. Generally, there is evidence that dependence exists between radiation energy and radiation RBE where lower energy radiations tend to have a greater biological effect than higher energy radiation. Specifically, the radiations of tritium and carbon K-shell x-rays have been studied in numerous experiments and the biological effects of both of these radiations are consistently greater than that of Co-60. In this work, the relationship between radiation energy and radiation effect has been investigated with the use of a newly developed double strand break (DSB) yield estimation algorithm. This algorithm makes use of a detailed solenoidal 30 nm DNA chromatin model to describe the radiation-sensitive biological target. In addition to the DNA model, NOREC, an event by event Monte Carlo code, was used in this algorithm to characterize the electron track. As an alternative to the conventional approach of computationally simulating DNA damage by spatial overlay of an electron track on DNA, this algorithm instead focuses on quantifying the distance between ionizations in an electron track and next determining the likelihood that any given ionization pair forms a DSB. The first step of the algorithm involves electron characterization while the second step relies on DNA molecule characterization. By assuming a DSB biological endpoint and determining the DSB yield as a function of electron energy, energy dependent RBE values were estimated for monoenergetic electrons from 10 eV to 1 MeV. Photon RBE values, x-ray RBE values and radionuclide RBE values were also calculated and reported in this work in addition to electron RBE values. Photon RBE values were estimated based upon the electron RBE calculation. Photon RBE values were reported from 1 eV to 10 MeV. In turn, x-ray RBE values were calculated based upon photon values for several tube voltage and filter combinations. Finally, RBE values for over 1000 radionuclides were estimated and reported.

Approximately 45% of men will develop cancer during their lifetime; some of which will be of reproductive age (Canadian Cancer Society, 2008). Current advances in treatment regimens such as radiotherapy have significantly lowered cancer-related mortality rates; however, one major quality-of-life issue in cancer survivors is the ability to produce healthy offspring. Exposure to ionizing radiation (IR) leads to genomic instability in the germline, and further to transgeneration genome instability in unexposed offspring of preconceptionally exposed parents. The results presented in this thesis define, in part, the molecular consequences of direct and indirect irradiation for the male germline. Direct exposure results in a significant accumulation of DNA damage, altered levels of global DNA methylation and microRNAome dysregulation of testis tissue. Localized cranial irradiation results in a significant accumulation of unrepaired DNA lesions and loss of global DNA methylation in the rodent (rat) germline. Biological consequences of the changes observed are discussed. / xii, 121 leaves : ill. ; 29 cm.