Hormones regulate numerous biological processes. Endocrine disrupting compounds (EDCs) are chemicals which are capable of altering normal hormone signaling, and as a result may contribute to a wide range of adverse health effects. Mycotoxins are one group of compounds which remain to be extensively tested for endocrine disruption. These compounds are toxic secondary metabolites of fungi, which are ubiquitous in nature and may be present in the food and feed of humans and animals, respectively. This study has made use of human in vitro systems to assess the impact of mycotoxins on steroid hormone receptor and non-receptor mediated pathways. The mycotoxins tested included zearalenone (ZEN) and two of its metabolites, α- and β-zearalenol (α-and β-ZOL); alternariol (AOH); the trichothecenes deoxynivalenol (DON), T-2 and HT-2 toxins; ochratoxin A (OTA) and patulin (PAT). The bioassays used included reporter gene assays (RGAs) with natural estrogen, androgen, progestagen and glucocorticoid steroid receptors; and the H295R steroidogenesis model. Endpoints such as nuclear receptor transcriptional activity, receptor expression, hormone production, steroidogenic gene expression or cytosol protein expression were assessed. All of the mycotoxins tested had significant effects on one or more of these parameters when compared to controls. The human in vitro systems used in this thesis have proved very useful for assessing interferences with the endocrine system. As steroid hormones and steroid hormone action is critical to numerous normal biological processes, changes in the activity of steroid hormones due to interference by mycotoxins may serve as a discerning indicator of endocrine dysfunction. This knowledge on the mechanisms of action of various mycotoxins is valuable for risk assessment purposes, which are necessary in order safeguard humans and animals.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:676471 |
| Date | January 2014 |
| Creators | Frizzell, Caroline Margaret |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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