Thesis (DTech (Biomedical Technology))--Cape Technikon, 2001 / Ionising radiation has the ability to induce, inter alia, DNA damage and is well established as a causative agent of carcinogenesis and mutagenesis. The effects of high doses of short duration have been well documented, whereas the effects of continuous exposure to low doses of ionising radiation have not, nor are they as clearly understood and current risk estimates are largely extrapolated from high-dose data of atomic bomb survivors. This study evaluated the clastogenic effects of low dose ionising radiation on a population of bats (Chiroptera) residing in an abandoned monazite mine. Bats were sampled from two areas in the mine, with external radiation levels measuring around 20 µSv/h (low dose) and 100 µSv/h (high dose). A control group of bats was collected from a cave with no detectable radiation above normal background levels. The most frequently encountered genetic event in human malignancy is the alteration of the p53 gene. Mutant p53 proteins have a longer half-life than the wild-type variant and accumulate to high levels in the nucleus of tumour cells. The study showed that not only was there a significant increase in p53 positive cells of radiation exposed bats, but also in the degree of positivity, especially in the cells lining the bronchioles of the lungs. Although experimental studies have shown that exposure to radiation may lead to the onset of fibrosis and an inflammatory response in the lung and other tissues, the magnitude of the dose exposure was not comparable to this study and histological examination of bat lung and liver tissues showed no morphological changes in radiation exposed bats when compared to the control group. It has been documented that chronic radiation exposures may give rise to a number of specific haematological defects which are collectively termed "preleukemia" or myelodysplastic syndrome. Full blood counts on bat samples showed a significant decrease in the MCV indicating microcytic erythrocytes from the radiation exposed bats. Differential counts performed on the peripheral blood of the bats showed a marked neutropenia. Neutrophils also showed marked dysplasia including psuedo-Pelger Huet cells in radiation-exposed bats. Cytochemical analysis using DAB myeIoperoxidase showed that control bats had hypogranular neutrophils andradiation-exposedbats had largely '1granularneutrophils. Bonemarrow biopsies were taken from both control and radiation-exposed bats and evaluated for ceIlularity, granulocyte: lymphocyte: erythrocyte (GLE) ratio and megakaryocyte morphology. A hypocelIular bone marrow, a decreased granulocytic haematopoeisis and dysplastic megakaryocyte morphology were observed in radiation-exposed bats. Mineralisation of bone osteoid was determined using image analysis and showed a highly significant decrease in the bone matrix from radiation-exposed bats. All haematological features observed are congruent with current literature describing secondary (radiation-induced) myelodysplastic syndrome.

Most breast cancer patients undergo radiation diagnostics and are also treated with radiotherapy. In addition to being an important treatment modality, ionizing radiation (IR) is a potent tumour-causing agent that has been linked to breast cancer development. However, the exact molecular etiology of IR-induced mammary gland carcinogenesis remains unknown. We set out to analyze the role of DNA methylation in mammary gland responses to low dose IR using a well-established rat model. We also studied low dose IR effects on global gene expression and microRNAome. We found that exposure to low, mammography-like dose of IR led to a significant loss of global DNA methylation in rat mammary gland tissue. Furthermore, low dose IR significantly affected rat mammary gland transcriptome and microRNAome. The datasets generated within the scope of this thesis may be used to identify novel predictive biomarkers for assessment of the magnitude of IR effects on mammary gland tissue. / xi, 120 leaves ; 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.