The ultrastructural effects and immunolocalisation of fumonisin B1 on cultured oesophageal cancer cells (SNO)

Introduction Cancer of the oesophagus (OC) follows the increasing incidence of cancer worldwide. There is a high incidence in the black population in certain parts of Transkei, South Africa and in parts of China; both have increased in recent times. Maize is the staple food of the population of Transkei. Fumonisins are mycotoxins produced by Fusarium verticillioides and other Fusarium fungi, found worldwide on maize and maize-based foods. Maize from an area of high OC incidence in the Transkei contained higher levels of fumonisin B1 (FB1) (44 ppm) than did commercial maize meal (<10 ppm). Fumonisin B1, a strongly polar compound, 5 is the most prevalent of the fumonisin mycotoxins. The polarity of the toxin determines its level of carcinogenicity i.e. the more polar the molecule, the greater the cytotoxic response. In addition to polarity, other determinants, such as the presence of a free amino group, carboxyl groups and the location of the hydroxyl group, could also affect the biological activity of these compounds. Thus, both the amino group and the intact molecule play an important role in the toxic and cancer-promoting activity of fumonisins. This would be compatible with the association of FB1 with both soluble and insoluble portions of the cell. 13 One of the established characteristics of fumonisin toxicity is its species specificity. A causal role of FB1 in equine leucoencephalomalacia, porcine pulmonary oedema, and liver and kidney carcinoma in rats has been reported. An initial study by Marasas et al. showed that BD IX rats chronically exposed to F. verticillioides developed oesophageal hyperplasia, forestomach papillomas and carcinomas, hepatocellular carcinomas and cholangiocarcinomas. Several subsequent studies with laboratory animals in which cultures of F. verticillioides or fumonisins were fed found no signs of cancerous or precancerous lesions of the oesophagus, however. Thus, there is no consistent animal model to support the theory that FB1 may be related to human OC. In human health, the role of fumonisins is still unclear, but the consumption of Fusarium-contaminated maize has been correlated with human OC in areas of South Africa, China and other countries. The high incidence of OC in the Transkei has been demographically associated with a prevalence of FB1-contaminated corn. Although other factors, such as smoking, alcohol consumption and certain dietary and environmental components could be involved in the aetiology of the disease, several recent studies have implicated fumonisins as a possible contributing factor. Nitrosamines or other carcinogenic agents may be responsible for the increased incidence of OC in humans, with fumonisins contributing to the problem through their potent tumour-promoting activity. In a previous study, we showed that FB1 (2–34 μM), a type 2B carcinogen, was cytotoxic to cultured SNO oesophageal cancer cells. We speculate that FB1 would alter organelle ultrastucture in cultured SNO human oesophageal cells. In this study, the SNO epithelial cell line (cells that retain most of the functions associated with primary cells), derived from a well-differentiated squamous cell carcinoma explanted from a 62-year old indigenous black male, was used to determine the effects of FB1 on cellular ultrastructure. The pathological changes induced by FB1 were determined using transmission electron microscopy. The cells were then immunocytochemically probed for the presence of FB1.