Radiation-induced epigenome deregulation in the male germline
University of Lethbridge. Faculty of Arts and Science
Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2008
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.
Dissertations, Academic , Radiation carcinogenesis -- Animal models , Radiation carcinogenesis , DNA -- Effect of radiation on , Cancer -- Radiography -- Complications -- Research , Germ cells -- Effect of radiation on