Document Type

Theses, Ph.D

Rights

This item is available under a Creative Commons License for non-commercial use only

Disciplines

Environmental sciences

Publication Details

Successfully submitted for the award of Doctor of Philosophy (Ph.D) to the Dublin Institute of Technology, May, 2010.

Abstract

Skin cancer is a global epidemic that is increasing annually. However, our knowledge of the mechanisms involved in skin carcinogenesis is relatively poor. Investigative studies to date have predominantly employed fluorescent UV A and I or UVB lamps. The information gained from such studies has pioneered this area of research effectively, however, the typical unimodal Gaussian distribution of such irradiators do not reflect that of solar radiation nor do they account for potential waveband interactions. Advancing technologies in solar simulation have opened up this field to more environmentally and biologically relevant exposures, not only in terms of distribution but also irradiance. To begin, this study addressed issues regarding the biological relevance of four different irradiators with respect to solar radiation. During this investigation the different exposure media employed (cell culture medium and PBS) were found to elicit significantly different results in terms of cell survival which were in direct conflict with the transmittance properties of the exposure media. The differential effects of the media were further investigated using endpoints that assessed the role of reactive oxygen species, mechanistic processes ( caspase-3 activity, mitochondrial membrane potential) and genomic perturbations (mitotic index, comet assay) in response to solar simulated irradiation. These results prompted further investigations into the effects of solar simulated radiation on cell culture medium. Medium transfer experiments showed that cell culture medium irradiated in the absence of cells was cytotoxic to unirradiated cells. Solar simulated radiation induced bystander effects were also investigated to determine if the presence of cells during irradiation had an effect on the cytotoxicity of the irradiated medium. Thus, this study assessed the two most fundamental parameters in non-ionising radiation in vitro investigations in order to form solid foundations upon which more detailed investigations into the mechanisms of skin carcinogenesis can confidently be performed.