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, November, 2010.

Abstract

The central objective of this study was to assess solar radiation-induced changes in cellular function, mitochondrial function and mitochondrial DNA to further investigate the role of these energy-dedicated and metabolically essential organelles in the response to the main environmental stressor associated with skin cancer initiation. An in vitro approach was chosen employing the human malignant melanoma (A375) and human amelanotic melanoma (C32) cells and the human spontaneously immortalized keratinocytes (HaCaT). A Q-Sun Solar Simulator was used to expose cells to low-level simulated solar radiation (SSR) as it provides a mimic of solar radiation that is environmentally relevant in the UV spectrum. Cell viability, apoptosis, DNA and protein content were analysed as cellular response end-points and they have been observed to change in a cell type-specific and time- dependent manner post SSR. Increases in mitochondrial genome number and mtDNA3895 were observed as an early response to low-dose SSR in human skin cells. The common deletion mtDNA4977t,h ough detected, did not directly increase in frequency with solar radiation exposure though the mtDNA3895 deletion, previously found to be associated with solar radiation exposure, was observed to be substantially increased in a cell-type and dose-dependent manner in skin cells post SSR. Impaired mitochondrial bioenergetics, dynamics and recycling may play a significant role in the melanoma tumour initiation and progression in humans post systematic solar radiation over-exposure. Furthermore the sensitive nature of the mitochondrial population of skin cells should not be underestimated as dynamic changes in their biology are evident even in cell populations that received low level irradiation of simulated solar radiation.