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

[摘要] The fumonisin mycotoxins are known to be the causative principle for several animaldiseases and are associated with the development of liver and oesophagus cancerand neural tube defects in humans. The thesis focuses mainly on thecharacterisation of the compounds from maize cultures of the fungus Fusariumverticillioides, isolated from maize, the toxicological effects in animals, mechanisminvolved in hepato- and nephrocarcinogenicity and discussing the major differencesand contradictions in the literature together with their impact on setting relevant riskassessment parameters to safeguard human health. Controversies include theimportance of non-genotoxicity vs genotoxicity in the development of cancer, the roleof threshold effects in carcinogenesis and the establishment of realistic riskassessment parameters that will also be applicable in developing countries. Recentapproaches suggest that thresholds should also apply for genotoxic carcinogens asinteraction with the DNA is only one event in the multi-step process of cancerdevelopment and therefore could not be taken as the basis for applying a no-effectthreshold 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 riskat any level due to additive or synergistic interactions with other xenobiotics and/ordietary constituents. The underlying mechanisms of fumonisin-inducedcarcinogenicity includes the disruption of sphingolipid, phospholipids and fatty acidmetabolism, which plays a major role in the modulation of apoptotic and cellproliferative pathways related to cancer development. Interactive responses betweenarachidonic acid and ceramide affect downstream cell signal transduction pathwaysand depending on the cell type the disruption of these pathways could eitherstimulate or inhibit cell proliferation which eventually will determine the induction ofapoptosis and hence affect cell survival. The modulating roles of dietary constituentssuch as vitamins, protein and the South African herbal teas are also highlighted asthey affected the outcome of toxicological assays, thus determining thresholds of theadverse effects in specific target organs that will impact risk assessment parameters.Regulation of the fumonisins in food and the associated risk are debated from manyperspectives. In developing countries there is a lack of quality control implying thatmaize highly contaminated with mycotoxins may directly enter the food chain ofadults and children as control of mycotoxins is difficult or in some cases totallyabsent. The interaction of politics, economy and technology will eventually determinethe impact on health as the regulation of fumonisin in food differs between countries.Knowledge about the biological effects of the fumonisins is currently playing animportant role in the development of simple and inexpensive methods to reduce thelevels of the fumonisin in maize by targeting specific populations at risk.

[发布机构] Stellenbosch University