Mycotoxicological properties of fusarium verticillioides and the fumonisins : mechanisms and implications for setting risk assessment parameters in humans

Thesis (DSc (Biochemistry))--Stellenbosch University, 2009.The fumonisin mycotoxins are known to be the causative principle for several animal diseases and are associated with the development of liver and oesophagus cancer and neural tube defects in humans. The thesis focuses mainly on the characterisation of the compounds from maize cultures of the fungus Fusarium verticillioides, isolated from maize, the toxicological effects in animals, mechanism involved in hepato- and nephrocarcinogenicity and discussing the major differences and contradictions in the literature together with their impact on setting relevant risk assessment parameters to safeguard human health. Controversies include the importance of non-genotoxicity vs genotoxicity in the development of cancer, the role of threshold effects in carcinogenesis and the establishment of realistic risk assessment parameters that will also be applicable in developing countries. Recent approaches suggest that thresholds should also apply for genotoxic carcinogens as interaction with the DNA is only one event in the multi-step process of cancer development and therefore could not be taken as the basis for applying a no-effect threshold for genotoxins. It would appear that a carcinogen such as fumonisin, whether it is labeled genotoxic or non-genotoxic per se, exhibits some degree of risk at any level due to additive or synergistic interactions with other xenobiotics and/or dietary constituents. The underlying mechanisms of fumonisin-induced carcinogenicity includes the disruption of sphingolipid, phospholipids and fatty acid metabolism, which plays a major role in the modulation of apoptotic and cell proliferative pathways related to cancer development. Interactive responses between arachidonic acid and ceramide affect downstream cell signal transduction pathways and depending on the cell type the disruption of these pathways could either stimulate or inhibit cell proliferation which eventually will determine the induction of apoptosis and hence affect cell survival. The modulating roles of dietary constituents such as vitamins, protein and the South African herbal teas are also highlighted as they affected the outcome of toxicological assays, thus determining thresholds of the adverse effects in specific target organs that will impact risk assessment parameters. Regulation of the fumonisins in food and the associated risk are debated from many perspectives. In developing countries there is a lack of quality control implying that maize highly contaminated with mycotoxins may directly enter the food chain of adults and children as control of mycotoxins is difficult or in some cases totally absent. The interaction of politics, economy and technology will eventually determine the impact on health as the regulation of fumonisin in food differs between countries. Knowledge about the biological effects of the fumonisins is currently playing an important role in the development of simple and inexpensive methods to reduce the levels of the fumonisin in maize by targeting specific populations at risk