Biochemistry

The Subprogramme is involved in an ongoing research effort aimed at improving national health by addressing issues on food safety and security.

Investigations of the contamination of food resources by fungal toxins and carcinogens, especially in staple diets such as the home-grown maize in rural communities of the Transkei region have been and remain a focus of research effort within the Subprogramme. The aim of the Subprogramme is to obtain exposure assessment data on toxins and carcinogens (especially the fumonisins), thus providing an indication of the health risks posed to communities by individual toxins which may contaminate staple food supplies and hence threaten food security.

The projects and activities of the Subprogramme Biochemistry are divided into three areas:

Identification and Human Exposure to Food- and Water-borne Toxins
The aim of these projects is to assess human exposure to harmful compounds which may occur in food or water supplies. Particular attention is directed at the toxic and carcinogenic compounds of fungal and algal origin. Areas of research activity include:

• Qualitative and quantitative determination of a diverse range of toxins and carcinogens in fungal cultures, cereals and food and water samples to assess human exposure, ie fumonisin analogues in maize, patulin in apple juice products and aflatoxins in areca nuts.
• Qualitative and quantitative determination of toxin residues in human and animal tissues to assess exposure of populations to contaminated foods and feeds.
• The improvement of existing or development of innovative methodology for the analytical determination of important relevant toxins.
• The isolation and structure determination of unknown toxins and carcinogens from fungi isolated from food.
• The isolation and chemical synthesis of toxins and carcinogens for use in animal experiments, biochemical investigations and as reference standards in analytical procedures.

Biochemical Action of Food-borne Toxins
The aim of this project is to investigate the biochemical mechanisms of action of food-borne toxins. These observations are essential in attempts to extrapolate observations made on experimental animals to humans. Current areas of research activity involve investigations into the toxicokinetics, toxicodynamics and biochemical mode of action of food-borne fungal toxins, especially the fumonisins, which occur at extremely high levels in home-grown maize consumed as the staple diet in the Transkei by Xhosa-speaking people at high risk for oesophageal cancer.

• Toxicokinetics: 
  Studies of the uptake, distribution, metabolism and excretion of toxins in different animal species.
• Toxicodynamics: 
  Studies of the biological responses of different animals to food-borne toxins and the time course of the resultant pharmacological or toxic responses.
• Biomarkers of Exposure: 
  Studies on biological markers for exposure of human populations to mycotoxins. By understanding the above mentioned processes and mechanisms, the feasibility of putative biomarkers for fumonisin exposure in human populations will be investigated with the aim of developing improved methods for the assessment of individual risk from fumonisin exposure in these populations. Previous studies have demonstrated that fumonisin exposure in a number of animal species results in a disruption of sphingolipid metabolism. The inhibition of a critical enzyme in de novo sphingolipid biosynthesis results in elevations in tissue, serum and urinary sphinganine levels. By appropriate animal studies with known doses of toxin and by selected surveys of human populations exposed to fumonisins, the potential use of the serum sphinganine:sphingosine ratio as such a biomarker is being investigated.

Risk Assessment Related to the Use of Indigenous Plants for Medicinal Purposes
The aim of this project is to investigate the health risks associated with human exposure to plants consumed for medicinal and dietary purposes in high oesophageal cancer prevalence areas. Initial investigations will focus on an epidemiological study to ascertain the nature and type of indigenous plants used by rural communities, while subsequent studies will be aimed at assessing potential toxicity or carcinogenicity of these plants and subsequently identifying the active compounds involved.