Proteomics as a tool to gain more insight into sub-lethal toxicological effects

This thesis focuses on a modern analytical method, proteomics, to investigate its use in the field of toxicological research. Proteomics is a high resolution method which separates all proteins present in a sample at a clearly defined state and compares this pattern to another one, under slightly different conditions (e.g. after exposure to a chemical). Protein changes may give rise to or reflect disease/harm of the individual and can be attributed to alterations in body functions/regulation systems. Analysis conditions and different varieties of proteomic methods are explained, and a brief introduction given where proteomics is already applied in toxicology. A specific investigation has been performed with the flame retardant HBCD (i.e. hexabromocyclododecane). It is a compound that accumulates in lipid tissue from where it is only slowly removed. Its mechanism of action is not yet completely understood and sometimes seems to be contradictory. Rats were exposed to HBCD in very low doses for just one week and liver proteins were compared to those of unexposed animals. As HBCD is suggested to disturb the thyroid system, both healthy and hypothyroid rats were investigated, of both genders. In female rats, not in males, some specific liver protein changes were seen in glucose/carbohydrate and lipid metabolism, and also in some stress related proteins. Changes were not dependent on the thyroid function of the females. These results are in line with previous findings that female rats were more susceptible to HBCD than males. In a further step, protein patterns of unexposed animals of both genders were compared, revealing gender-dependent differences that exceeded the effects seen in any of the other comparisons, mainly in the pathways that were also affected by HBCD in females. A previous proteomic study on serum proteins has also shown clear gender-dependent concentration differences in rats. This underlines the importance of performing studies both in female and male individuals. The detection of considerable gender-dependent protein alterations confirms that proteomics is a biochemical tool with high sensitivity and large potential also in toxicological research.