Wang, Yanfei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 135-148). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Thesis (MScAgric)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.

Despite the medical advancements, the woman breast cancer incidence rates keep rising in the past few decades. Scientists have proposed the increased exposure to endocrine disrupting chemicals as a possible factor for the rises. Zearalenone (ZEA) and aflatoxin B1 (AFB1) are common mycotoxins that are present in cereal crops worldwide. ZEA has long been recognized as a xenoestrogen, while the endocrine disrupting effects of AFB1 on steroidogenesis have been identified recently. Due to the co-occurrence and the endocrine disrupting potentials of ZEA and AFB1, the hypothesis of this project was proposed as exposure to low doses of ZEA and AFB1 might affect the growth of hormonal dependent breast cancer. In order to address the hypothesis, the aim of the first study was to examine the ultimate effects on growth and cell cycle progression in breast cancer MCF-7 cell line, following low dose exposure to ZEA and AFB1 individually and in combination. The effects on viability, cell growth, DNA synthesis, cell cycle progression and cyclin gene expressions were determined. Significant interactions were detected for their effects on viability and DNA synthesis. While ZEA promoted growth, DNA synthesis and cell cycle progression in MCF-7 cells, AFB1 was cytotoxic and counteracted the effects of ZEA. This study confirmed the growth promoting properties of ZEA, and is the first to report the combined effects of ZEA and AFB1 on breast cancer cell growth, suggesting endocrine-disrupting mycotoxins that co-occur in human food can interact and modulate the effects of each other on human health. The second study aimed to reveal the modulation of breast cancer genes and the underlying pathways that were directly affected by ZEA and AFB1. By using a real time reverse transcription polymerase chain reaction array, it was shown that ZEA was capable of altering the expressions of a large number of breast cancer related genes, whereas AFB1 had minimal effects on the breast cancer gene expressions. With the use of specific inhibitors, estrogen receptor α, G protein-coupled estrogen receptor 1, and mitogen-activated protein kinases (MAPKs) were found to be responsible for ZEA’s effects on cell growth and myelocytomatosis oncogene activation; while MAPK pathways might be involved in the cytotoxic effects by AFB1. Further confirmation is necessary for linking the activations of estrogen receptors and MAPKs to breast cancer cell growth by ZEA and AFB1. The last study aimed at assessing the impacts of ZEA and AFB1 on steroidogenic and steroid metabolic enzymes in MCF-7 cells, which might result in hormonal imbalance and undesirable breast cancer cell growth. By evaluating the mRNA expressions, it was found that ZEA significantly modulated the expressions of all the steroidogenic and steroid metabolic enzymes tested while AFB1 altered the expression of cytochrome P450 (CYP) 1A1 and CYP 1B1. Coexposure of MCF-7 cells to the two mycotoxins revealed that AFB1 antagonized the effects of ZEA on expression of CYP 1A1, CYP 3A4 and CYP 1B1. Further research into the alternations of enzyme levels and activities by ZEA and AFB1 is necessary before a solid conclusion can be made. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

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Thesis (M.Sc. (Experimental Pathology))--Mahidol University, 1971.

Thesis (M.Sc.(Chemistry))--University of Pretoria, 2001. / Includes abstracts in English and Afrikaans. Includes bibliographical references.

The literature on the synthesis of tremorgenic indoles is reviewed in Chapter 1. These compounds are of great importance to agriculture, especially in New Zealand and the United States of America, as they affect the central nervous system of livestock grazing infected pastures. The research centres on the synthesis of lolitrem B, a ten ring structure containing a central indole moiety. The central indole moiety is common for all of the tremorgenic indoles. To this end, studies on the preparation of a trans-fused hydrindane system and its incorporation into the central indole moiety are discussed in Chapter 2. Chapter 3 details investigations into the preparation of a pyrrole from a model used for the hydrindane system. Once obtained, the pyrrole is modified to give the pyranopyrrole, which, in turn, is reacted with dienophiles in Diels-Alder cycloadditions to give substituted indoles. Utilising the model for the hydrindane, studies on the Fischer indole reaction were undertaken to give substituted indoles. Modification of these led to the synthesis of the left-hand side of paspalitrem B. This work is discussed in Chapter 4. Preparation of the tetrahydrofuran portion of lolitrem B and incorporation onto the central indole moiety is detailed in Chapters 3 and 4.

Maize (Zea mays L.) is an important cereal world-wide, serving as seed for growers, food for man and livestock as well as an industrial raw material. Unfortunately, it is also a suitable substrate for growth, development and activity of spoilage fungi. Fungal growth is a major problem in cereal grains throughout the world and may lead to poor quality of the products, as well as adverse effects to human and animal health due to mycotoxin production. Maize is usually harvested at high moisture content and then dried to bring down the moisture content to a safe level before storage. Delay in drying to safe moisture levels increases risks of mould growth and mycotoxin production. In rural villages maize is dried using only sun drying and they rely on sacks, thatched silo and drums as their storage facilities. This is insufficient to prevent damage by insects, rain, and rodents, which in turn allows fungi to invade these storage facilities. Maize was sampled in two rural areas of Venda (Limpopo Province) and the percentage moisture content was determined and then screened for total fungal contamination. The samples were also analysed for mycotoxins that have been reported to commonly occur in maize. There was no significant difference in the extent of fungal contamination in Mapate and Folovhodwe villages. Of the fungal species detected, Aspergillus species were the most common with Aspergillus flavus being the most predominant. On analysis by the multi-mycotoxin screen, aflatoxin had the highest incidence amongst mycotoxin, followed by T-2 toxin. However on using the VICAM method of analysis aflatoxins, deoxynivalenol and fumonisin were the most predominant mycotoxins in the samples, while zearalenone toxin was also amongst predominant mycotoxins but with the highest level of 0.1 ppm. Most of the mycotoxin-containing extracts were found to reduce the % cell viability of human lymphocytes, after 24 hours of incubation as determined by the methyl thiazole tetrazolium salt assay. vii In conclusion the co-occurrence of these toxins in maize and maize meal may highlight the problems associated with the intake of numerous toxins that could in turn lead to more adverse health effects such as liver, oesophageal, breast and cervical cancer, male reproductive tract damage and gynacomastasia. There is, therefore, need to disseminate information to these people, using simplified methods such as programs on radio and televisions on mycotoxin hazards and discussion on the issue should also feature regularly on daily newspapers and magazines, about the dangers and management aspects of mycotoxins, and the susceptible produce. / Prof. M. F. Dutton Mr. F. E. van Zyl