MRC PhD students

Ms H Burger is currently registered as a PhD student at the Department of Biochemistry, University of Stellenbosch under the supervision of Profs WCA Gelderblom and P Swart.  The title of her thesis is: “Investigations into possible mechanisms involved in the induction of cancer by fumonisin B1 (FB1), by using a hepato- and oesophageal carcinoma cell-model.” 

Fumonisin B1 (FB1), a natural occurring mycotoxin produced by the fungus Fusarium verticillioides in maize is known to causes several diseases in animals and is associated with a high incidence of human oesophageal (OC) and liver cancer as well as the development of neural tube defects in certain geographical areas in the world. The contamination of maize by this fungus in developing countries is therefore recognised worldwide as major health problem, especially in the former Transkei region where a traditional staple diet of maize is consumed. Recently, the alteration of cellular lipid biosynthesis has been proposed as a possible mechanism for cancer promotion by FB1. 

The present study will be undertaken to investigate the effect of FB1 on lipid profiles of liver and oesophageal carcinoma cells in order to provide more information about the possible role of these changes in the carcinogenic properties of this mycotoxin.  Because of the disruptive effect of FB1 on the lipid metabolism as shown by previous studies, it is therefore pertinent to examine lipid parameters of membrane microdomains, such as lipid rafts.  Lipid rafts are small membrane microdomains or platforms that are enriched in sphingolipid and cholesterol and play an important role in many cellular processes such as signal transduction; membrane fusion; membrane budding and protein trafficking.

At present little is known about the effect of FB1 exposure on lipid rafts.  In addition to this is the effect of FB1 on 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in endogenous cholesterol biosynthesis. Recent studies showed that serum cholesterol was increased in experimental animals. Most mammalian cells obtain cholesterol by internalization of cholesterol by plasma lipoproteins or its de novo synthesis in the endoplasmic reticulum. As HMG-CoA reductase plays an important role in the regulation of cholesterol homeostasis, the effect of FB1 on the activity of this enzyme will be monitored.

Supervisors: Profs WCA Gelderblom and P Swart