Title:
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An investigation of food and feed based mycotoxins as potential endocrine disrupting contaminants
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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.
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