Experimental Carcinogenesis

The main objectives of the Subprogramme include:

To develop basic strategies for (i) risk assessment of naturally occurring food borne carcinogens and (ii) the cancer chemopreventive properties of dietary constituents. Studies entail investigations on the mechanisms of the induction and/or inhibition of cell growth, dose response effects and biomarkers related to the carcinogenic process. An integrated approach utilizing in vitro cell culture systems and animal cancer models provides an ideal platform to investigate mechanisms of carcinogenesis and models for chemoprevention.

 Diet, Nutrition and Cancer          
In order to design better and more effective nutrition intervention and educational programmes, adequate information on the existing nutritional status and specific nutritional problems in South Africa is needed. Unique features of such studies are that they address human heterogeneity as well as ethnic differences. The resultant nutritional epidemiology provides a unique opportunity to study, not only dietary and nutritional factors, but also other risk factors associated with OC risk in different geographical areas in southern Africa.

• Cancer Chemoprevention
• Cancer modulating properties of the South African herbal teas

The interest in the health benefits of tea has emerged during a period of intensive research on polyphenolic flavonoids and their potential anticancer properties. Rooibos and honeybush are herbal teas endemic to South Africa and their health beneficial properties are investigated. Rooibos contains the dihydrochalcones, aspalathin and nothofagin, while honeybush contains a variety of polyphenols of which the xanthone, mangiferin and the flavanone, hesperidin are the major phenolic constituents.

• Dietary fatty acids and cancer

Dietary polyunsaturated fatty acids (PUFA) are known to modulate the cell membrane phospholipid composition play a key role in intracellular signaling pathways. Fatty acids such as arachidonic acid (C20:4n-6) and eicosapentaenoic acid (C20:5n-3) can act as second messengers, i.e. molecules acting in a reversible manner at a precise intracellular location for a very short time to amplify or attenuate a signal. Different signalling pathways regulate all the critical phases of cell growth including cell proliferation, differentiation, and apoptosis. Furthermore, the modulation of cellular oxidative status by dietary PUFA and effect on cell growth and survival is an important process with regards to cancer development.

Food-borne Carcinogenesis
FB1 has been classified as a class 2B (possibly carcinogenic) carcinogen to humans. Mechanistic studies in animal models in vivo and cell culture systems in vitro showed that FB1 is a weak cancer initiator but a strong cancer promoter. Several studies suggested that cancer initiation by this apparent non-genotoxic carcinogen is related to oxidative damage. The inhibition of hepatocyte cell proliferation has been suggested to be the event occurring during cancer promotion. Several mechanisms have been proposed of which the disruption of sphingolipid or phospholipid and fatty acid metabolism are regarded as the most likely.
Differences exist when considering and implementing risk assessment parameters for the fumonisins from a global perspective to remote microenvironments in developing countries where maize is the sole dietary staple. The health risk posed by the fumonisins depends on variations in the maize consumption patterns which differ not only between the various ethnic groups but also the resultant migratory patterns, e.g. major differences exist between black South Africans living in rural areas as compared to the more urbanized regions.

Isolation and Purification of Mycotoxins
Since the discovery of the fumonisins in 1988 by scientists at PROMEC, world-wide interest arose in the natural occurrence and toxicology of these toxins that are produced by Fusarium verticillioides. Fumonisins are marketed as analytical standards both locally and abroad to world-renowned research centers.