In human monitoring procedures, measurements obtained from endpoints to determine genetic damage are sometimes referred to as biomarkers. Depending on their nature, they may be biomarkers of exposure, effect or susceptibility. A causal relationship has been proposed for cytogenetic damage in peripheral lymphocytes and subsequent cancer risk. Biomarkers include measurements of chromosome damage using fluorescence in situ hybridisation (FISH) techniques, altered levels in serum of ras p21 oncoproteins or p53 tumour suppressor genes and DNA strand breakage in the single cell electrophoresis assay (Comet assay). Damage can be measured in individuals of different metabolic genotypes or different disease states, such as respiratory diseases (lung cancer patients, chronic obstructive pulmonary disease and asthma), diabetes, etc. As well as for the examination of somatic cells (human lymphocytes), the Comet assay can also be used effectively in human sperm to give some measure of DNA integrity in future generations. The effect of an individual’s genetic constitution and lifestyle e.g. diet, smoking and drinking habits can also affect responses. In addition, the signalling pathways of genotoxic agents will be examined for the DNA and RNA expression on different types of diseases.
The proposed studies would examine the effects of various agents, after in vitro exposure, primarily in human blood, but also in serum and sperm, to determine the contribution of the various biomarkers on the disease states. Responses would be compared with effects in healthy individuals as well as the confounding effects of the individual’s genetic constitution and lifestyle. In the first instance the disease of various cancers would be investigated, but other disease states could also be considered.
This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee also applies in addition to tuition fees.