PROMEC Unit
Current projects
Project 3830: Occurrence and Toxigenicity of Food-borne Fungi
The project aims to continue to identify food-borne fungi in samples of staple foods obtained from national and international commercial and home-grown sources that present a threat to human health. Food-borne and pathogenic fungi are identified, pure cultures are prepared and preserved and taken up in the MRC PROMEC Unit culture collection. The culture collection has been computerised on a specially designed database (DBText Works), and has been updated to a Windows environment and redesigned to include chemical data relating to the stored fungi. Toxicity testing, in support of many of the PROMEC Unit’s and collaborative projects, will continue, and the presence and levels of mycotoxins chemically confirmed by the subprogramme Biochemistry in the PROMEC Unit. Continuation of these functions is imperative to the PROMEC Unit and several national and international collaborators and stakeholders, as well as several new proposals currently under consideration.
Research into mycotoxins that have national and international implications, including fumonisins, patulin and aflatoxin, has been undertaken and future research directions determined accordingly. Investigations into the fumonisin producing fungal isolates in the PROMEC Unit’s collection and isolates from Transkeian maize samples will continue. This is very important in order to find good producers of the toxin for large scale production of fumonisins for experimental purposes and the commercial market. Further investigations into the viability and purity of fungal cultures preserved in the culture collection will continue.
Previously no information regarding patulin producing fungi in South Africa existed and collaborative studies with the apple industry indicate that Penicillium expansum, a patulin-producing and post-harvest rotting fungus, is prevalent in South Africa in naturally infected apples. The incidence of other patulin producing fungi in South Africa has also been established, and guidelines and procedures that should decrease residual levels of patulin in juiced products intended for human consumption have been put forward to industry. Training of apple sorters with regard to patulin producing fungi and their symptoms in the fruit has been requested by local manufacturers and will continue. In an extensive experiment on the down-line processing of apple juice, results indicate that there is a significant reduction in fungal counts and the levels of patulin by the addition of activated charcoal, but none of the other down-line processes had a significant influence on the levels of patulin in the final concentrated juice. The role of the pasteurization process on the fate of the organisms in apple juice and on the levels of patulin is under investigation.
Due to the adverse clinical effects, such as oral submucous fibrosis (OSMF) and cancer, associated with the chewing of areca nuts and the possible contributory and/or synergistic effects that mycotoxins may have on carcinogenesis, collaborative research into the production of aflatoxin by Aspergillus flavus on areca nut has been undertaken. Aflatoxin producing strains of A. flavus have been isolated from commercially available areca nut, and the levels of aflatoxin B1 in most nut samples were higher than the legal foodstuff limit of 5 μg/kg. The results further indicate that the ability of A. flavus strains (originally isolated from maize or areca nut) to grow and produce aflatoxin on areca nut, is influenced by the type of nut and the cultural conditions. Investigations into the cultural conditions indicate that the relative humidity under which infected nuts are incubated are important for the production of aflatoxin. No aflatoxin could be found in areca nut mixtures used for entertainment purposes. Research is currently being completed in collaboration with the Faculty of Dentistry, University of Stellenbosch (US).
The antifungal activity of fumonisin B1 on the growth of several fungal species was tested by comparative gel-diffusion and disk methods. Three of the fungal species tested (Penicillium expansum, Alternaria alternata and Botrytis cinerea) were sensitive to fumonisin, whereas the fumonisin-producing species (F. verticillioides, F. proliferatum and F. globosum) were not. The effect of fumonisin B1 on the germination and viability of conidia of Fusarium and other fungal species as well as the viability of lyophilised conidia of Fusarium and Alternaria species with fluorescent and other stains have been investigated and the results are being submitted for publication.
Research on the effect of Bt-maize hybrids on the incidence of fumonisin-producing Fusarium species, stalk borers and the levels of fumonisin in naturally high Fusarium incidence areas in South Africa has successfully been contracted with Monsanto SA and concluded. Further research proposals on the effect of Bt-maize hybrids on the incidence of mycotoxigenic fungi and the levels of mycotoxins in South Africa, as part of a global investigation in which South Africa is one of five participating countries, have been entered into with Monsanto USA, and are being prepared for publication.
Project 3835: Studies on Pathogenic and Medically Important Fungi
Multi-centred clinical trials to investigate alternative treatments for dermatophytoses and onychomycoses, i.e. itraconazole in dermatophytosis (tinea pedis/manus/cruris/corporis) and onychomycosis; terbinafine in sporotrichosis, onychomycosis, tinea cruris/corporis and tinea capitis, have been completed. Comparative studies into the efficacy of itraconazole versus terbinafine in tinea pedis/manus have also been done. Studies into the clinical epidemiology, aetiology and ecology of pathogenic and medically important fungi, and to assess alternative treatment regimens for fungal infections in order to treat these infections more cost effectively and to prevent fungal infections in lower socio-economic population groups will continue. Further studies on Fusarium and other fungal species that are isolated from eye infections, particularly corneal ulcers, and a study into the incidence of food-borne hyphomycetes in immuno-compromised hosts and AIDS patients in South Africa will be conducted. Fully sponsored lectures on medically important fungi are being presented on a continuing basis to general practitioners and medical specialists as part of Continued Medical Education (CME) in South Africa.
A study to investigate the incidence of tinea infections in two schools in the Transkeian region of the Eastern Cape Province commenced in August 1997. During several visits approximately 650 children were examined and more than 150 specimens from infected children were taken. Results indicate that 15-20% of the total number of children attending these schools are infected with Trichophyton violaceum and that the children do not receive any treatment. Guidelines by means of pamphlets (in English and Xhosa) to reduce and prevent the spreading of these mycoses were given during follow-up visits to the schools. Negotiations with pharmaceutical companies to obtain sponsored treatment for the infected children have been successful and the treated children are being followed-up.
Contract work into the antifungal activity of Aloe bitter to the aetiological agents of dermatophytoses causing tinea pedis and tinea corporis has been successfully negotiated and completed with Simply Aloe South Africa. The success of this project has led to testing of several other compounds, including teas and mycotoxins, for antifungal activity with far reaching implications.
Project 3838: Surveillance of Fusarium Species and Fumonisins in Maize in Rural Subsistence Farming in the Transkei Region of South Africa
This project commenced in 1997 to investigate new mycotoxin surveillance strategies for homegrown maize in the Transkei region, in collaboration with Dr Ray Coker (Natural Resources Institute, University of Greenwich, UK). Attempts (Wellcome Trust and DFID, UK) to secure international funding were unsuccessful and the project became solely a MRC baseline-funded project, with field trips undertaken every three years, viz. 1997, 2000 and 2003. Approximately 80 maize samples were collected in Centane in 1997 and approximately 120 maize samples were collected from Bizana and Centane in each of 2000 and 2003. All households visited were recorded and mapped by GPS/GIS instrumentation.
This project was previously named as “Aetiology and Prevention of Oesophageal Cancer in the Transkei Region of the Eastern Cape Province”, but due the expansion of the Bt maize work under project 3830, and planning to introduce Bt maize in the rural Transkei, all future research on Bt maize will be included under this project.
It is aimed at, and directly involves subsistance farmers and households, in the rural communities of the Transkei region. These communities are in great need of assistance with regard to information, training and education concerning oesophageal cancer, other health problems associated with mycotoxins and better agricultural practices.
Project 3844: Fusarium verticillioides and Fumonisin Contamination of Commercial Maize in South Africa
This project formed part of a contract entered into with the Grain Crops Institute, Agricultural Research Council (GCI/ARC), Potchefstroom. Some 1400 maize samples, representing the 1995/96-1999/2000 crop seasons, have been analysed and the results sent through to the GCI/ARC. Two scientists from the ARC visited the PROMEC Unit to assess the inter- and intra rater analysis of the maize samples, and concluded that methods used in the PROMEC Unit to determine the incidence and identity of fungi present in the samples, are very reliable compared to other mycological methods. The GCI/ARC presented some of the results at a conference, but opted not to proceed with publication.
Project 3848: Production of Fumonisins by Fusarium verticillioides MRC 826
Fumonisins research has a great national, international and the PROMEC Unit’s in-house demand for this toxin for biological experiments to determine their carcinogenic and toxic effects. Fumonisin sales have thus far amounted to more than R3M (see Project 3820). Factors that influence mycotoxin production by Fusarium verticillioides under natural and experimental conditions are being investigated. Experiments on the influence of temperature, pH, moisture content and the influence of the addition of L-methionine, a fumonisin precursor, the ability of Fusarium species to utilise fumonisin B1 (FB1) as a carbon source and the effect of fumonisin on the germination of the spores of these fungi are currently being concluded and submitted for publication. A schedule to investigate several other factors that influence toxin production in vitro has been formulated.
In order to elucidate the mechanism by which Fusarium verticillioides produces fumonisins, a study into the gene regulation of fumonisin production is being done. Cultural mutation has often been found to occur when F. verticillioides is grown on media rich in carbohydrates and these mutations may involve loss of virulence and the ability to produce toxins. The fumonisin biosynthetic gene cluster consists of 15 genes, namely FUM genes. A set of F. verticillioides MRC 826 subcultures that were previously grown under varying cultural conditions, including diverse media, and were shown to exhibit fluctuating fumonisin levels is being studied. Quantitative Real-time PCR will be performed to ascertain whether the FUM genes are differentially expressed or absent in the strains with varying fumonisin profiles.
Phylogenetic analyses using DNA sequences of the FUM 1 and FUM6 genes are being performed on fumonisin producing Fusarium species of Section Liseola. Amplified Fragment Length Polymorphisms (AFLPs) were used to determine the genetic diversity and genetic relatedness of a set of F. verticillioides strains that exhibited various fumonisin profiles. This method is also used to aid in species identification. The purpose of this study is to elucidate whether the AFLP genotype corresponds with the fumonisin producing ability phenotype of the F. verticillioides strains. Application of this method has the potential to identify toxigenic species and replace the conventional methods that is currently a labour intensive and time-consuming task. Application of such methods will have far reaching implications in industry and the prediction of fumonisin levels that may be produced in contaminated maize.
AFLP analysis is also currently being used to determine the genetic diversity of Fusarium globosum strains, which were previously shown to be fumonisin producers. These results will give an indication of the means of reproduction, as low diversity will be an indication of clonal (asexual) reproduction, and high diversity will be an indication of sexual reproduction. It is important to determine the mode of reproduction, as meiotic recombination could result in the diversity of genes that govern traits involved in pathogenesis and toxin production.
SUBPROGRAMME: BIOCHEMISTRY OF FOOD-BORNE TOXINS
Project 3850: Identification of Food-borne Toxins and Carcinogens
This project involves analytical method development and chemical analysis of a diverse range of mycotoxins in food matrices. Research undertaken under this project led to the development of the first officially recognized HPLC method for determination of fumonisins in maize. As a consequence, the PROMEC Unit is recognized as a world leader in fumonisin analysis. This project continues to be involved in a wide range of activities related to food safety with respect to the natural occurrence of mycotoxins in foods and aspects of risk assessment. The PROMEC Unit acted as coordinator for one of the projects being undertaken as part of the Coordinated Research Programme (CRP) on Evaluation of Methods of Analysis for Determining Mycotoxin Contamination of Food and Feed being funded by the Food and Agricultural Organization (FAO) / International Atomic Energy Agency (IAEA) Training and Reference Centre. The project involved the development of a TLC method for the determination of fumonisin B1 in maize. It was successfully completed and the results analysed and reported to participants at a research meeting held in Cape Town. The method has now been published in an international journal.
Research has continued to establish human exposure to fumonisins via contaminated maize. This is currently an ongoing project performed in collaboration with other PROMEC Unit projects such as those involved with the collection of maize in the Transkei region (project 3865). Further field trips have been undertaken to sample maize, commercial maize products and cooked food samples from Bizana and Centane districts, Transkei region. These samples are currently being analysed for fumonisins. Analysis of fungal culture material in collaboration with the Microbiology subprogramme (project 3830) to determine the ability of various strains of Fusarium verticillioides to produce fumonisins is ongoing.
As part of a large international study being funded by Monsanto, maize harvested from field trials of cultivars containing the Bt gene and their non-Bt isolines has been analysed for fumonisins and deoxynivalenol. Similar studies on locally available commercial varieties are being conducted in collaboration with the ARC.
Further collaboration with Iranian workers was undertaken and two manuscripts concerning fumonisin contamination of Iranian maize and exposure assessments of the Iranian population have been published. An Iranian student has spent a six month period at the PROMEC Unit being trained in fumonisin and aflatoxin analytical methods. Iranian maize samples collected by the student have been analysed for these two toxins and a manuscript has been published. Collaborative studies have been concluded with partners in Brazil concerning the natural occurrence of fumonisins in maize samples collected in Santa Catarina, southern Brazil and in baby food products collected in Campinas, Brazil. These studies have resulted in a number of publications in international journals and conference presentations.
A study has been conducted into the fate of fumonisin during the preparation of porridge and a manuscript has been published. Further work is currently being undertaken with home-grown maize from Transkei. The production of the C series of fumonisins by various Fusarium species, as well as their natural occurrence, is being investigated by LC-MS analysis. A manuscript has been published and another is in preparation.
Further work was undertaken with industrial partners to investigate the occurrence and monitor the presence of patulin in apple juice and to investigate the efficiency of activated carbon to remove patulin during apple juice processing. The use of a commercial oxidising solution to sterilize deck stored apples has been investigated and a report presented.
Sorghum and pearl millet samples collected by collaborators in Mali have been analysed for fumonisins and moniliformin. Fusarium isolates from one each of the sorghum and millet samples have been cultured and tested for fumonisin and moniliformin production. This study is being extended to the determination of fumonisins in maize, pearl millet and sorghum collected in various districts of Nigeria where these crops are grown together to assess the relative susceptibility of the cereals to mycotoxin contamination. This study is funded by INTSORMIL.
The possibility of fumonisin contamination of South African wheat was investigated in collaboration with SA Grain Laboratories. Marogo samples were collected in Limpopo Province in collaboration with the Marogo Research Programme at North-West University.
Project 3851: Risk Assessment of the Ingestion of Plants for Medicinal and Dietary Purposes.
The analysis of the data from the epidemiological case-control study stratified by gender has revealed that of the 19 plants identified as being used for dietary purposes, five plants were highlighted as being of some concern. The plant Rumex lanceolatus presented with an almost two-fold increase in the risk of developing oesophageal cancer (Males: OR=1.86, 95% CI 1.31-2.63; Females: OR=1.68, 95% CI 1.18-2.41). The plants Raphanus nasturtio aquatica and Colocasia esculenta were also found to present an almost two-fold increased risk of developing OC, while Sida dregei presented a four- and two-fold increased risk in males and females respectively. Exposure to the plant Raphanus raphinastrum resulted in a 40% greater chance of developing OC in males and females.
Of the 29 medicinal plants investigated, four were highlighted as being a risk factor for the development of OC in both males and females. The mutagenic potential of these plants is being evaluated using the Salmonella reverse mutation assay on bacterial strains TA 97a, TA98, TA100 and TA102. This assay will indicate the plant's ability to alter the DNA of the bacteria either through frameshift mutations, base-pair substitutions and/or oxidative cell damage. Through the use of a metabolic activation system, it will be possible to identify direct-acting mutagens from promutagens in these plants.
Project 3855: Biochemical Action and Biomarkers of Food-Borne Toxins.
Blood and urine samples collected from over 150 volunteers in Bizana and Centane districts of the region are being analyzed for sphingoid bases as part of the investigation into the possible use of the sphinganine / sphingosine ratio as a biomarker for fumonisin exposure. In addition, blood and urine samples have been collected from individual households participating in the maize intake survey (project 3865) and are being analysed in order to investigate the possible use of the ratio on an individual basis to measure fumonisin exposure. Collaboration has been established with Prof Chris Wild, University of Leeds, to undertake further studies on possible fumonisin biomarkers and urine samples have been supplied to his laboratory.
The possibility of using hair or nail samples as a biomarker for fumonisin exposure is being further investigated. Initial animal studies on hair collected from rats and vervet monkeys receiving fumonisin-contaminated feed showed that analysis of fumonisins in hair is possible by LC-MS. Following the successful demonstration of the accumulation of fumonisins in hair of experimentally dosed animals, subsequent investigations have been extended to analyse composite human hair samples collected in barber shops in Bizana, Centane and Butterworth areas of the former Transkei region, as well as from individuals in selected households in the Centane district who were participating in the maize intake study (project 3865). In addition, nail samples were collected from the same individuals. Hair samples from eight individuals had a mean level of 21.6 μg/kg of hair with the highest level of 126 μg/kg and a corresponding nail level of 0.11 μg/kg from the same individual. A selection of nail samples obtained from volunteers in Linxian, China and sent to the PROMEC Unit by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) in the USA also showed FB1 to be detectable in this matrix. As a result of the publication of these results, a contract has been signed with NCI to undertake the determination of fumonisins in over 800 nail samples collected during the epidemiological investigations conducted by NCI in Linxian, China.
Project 3860: Human Exposure to Water-borne Microcystin Hepatotoxins
Collaboration with the Department of Chemistry at the University of Stellenbosch, has established the potential of heterogeneous photocatalytic oxidation for the purification of water supplies contaminated with the hepatotoxic microcystin algal toxins. A laboratory-scale ‘falling-film’ reactor based on fibreglass sheet impregnated with immobilised titanium dioxide has demonstrated the destruction of these toxins during irradiation with germicidal UV-C lamps. Input has been made into the development of a strategic initiative being undertaken on behalf of the Water Research Commission by Dr W Harding, DH Environmental Consulting. The results of this project have been presented at the recent International Conference on Harmful Algal Blooms.
Project 3865: Assessment of Fumonisin Exposure in Populations on a Maize Staple Diet in the Transkei Region of the Eastern Cape Province and KwaZulu-Natal
The aim of this project is to investigate the exposure of individuals to the fumonisin mycotoxins in selected districts of the former Transkei region of the Eastern Cape Province, namely the magisterial districts of Centane and Bizana. Previous studies in these districts involved the collection of home-grown maize and its analysis for fumonisin mycotoxins. This has been further extended to include a study of the actual dietary habits in the individual households as they relate to the cooking and consumption of maize with the aim of determining the actual maize intake by householders in these districts. Previous estimates have been based on 1977 carbohydrate intake data from mothers attending post-natal clinics in the Ciskei region. Field visits to the areas of interest have been made during 2000-2004 and data collected on maize consumption. Six professional nurses from the former Transkei region were trained at the PROMEC Unit to proceed with the study in the Centane and Bizana districts. Fumonisins have been determined in samples of home-grown maize, commercial maize meal and samp, as well as samples of cooked food, collected for fumonisin determination. This work also links with project 3850. In addition, the project links with project 3855 in that plasma and urine samples have also been collected for determination of sphingoid bases as possible biomarkers of fumonisin exposure. Processing of the data generated by the interviews and measurements in 100 households in Bizana and 70 households in Centane is underway and statistical evaluation of the results is being undertaken in preparation for publication of the data.
Collaboration has been established with agricultural economics researchers at the University of Pretoria aimed at the investigation and comparison of fumonisin levels in Bt-maize and those in landrace varieties as planted by subsistence farmers themselves in rural areas of KwaZulu-Natal and the Eastern Cape Province. The potential for reduced fumonisin levels in Bt-maize has been demonstrated in various studies around the world, as well as in some areas of South Africa. It is thus of importance to determine to what extent this could be a viable intervention measure for reducing mycotoxin exposure. This work is being funded by the Rockefeller Foundation.
Researchers from the PROMEC Unit have assisted in the project entitled “Mycotoxins, a food safety risk in Africa”, currently being funded by the Dutch Ministry of Agriculture, Nature Management and Food Quality, which also involves the Department of Agriculture in the Eastern Cape Province and the Agricultural Research Council.
SUBPROGRAMME: EXPERIMENTAL CARCINOGENESIS
Projects
Project 3875: Long-term Effects of Food-borne Toxins and Carcinogens in Experimental Animals
The hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides (= Fusarium moniliforme) strain MRC 826 in male BD IX rats were first reported by the PROMEC Unit in 1984. Subsequent chemical analyses of the fumonisin B mycotoxin content in the culture material used and long-term carcinogenesis studies with purified fumonisin B1 (FB1), provide information about dose-response effects, relevance of hepatotoxicity during FB1-induced carcinogenesis and the existence of a no-effect threshold. Fumonisin intake levels of between 0.09 to 0.16 mg FB/100g bw/day over a period of approximately two years effect liver cancer in male BD IX rats. Exposure levels below 0.09 mg FB/100 g bw /day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role on fumonisin-induced hepatocarcinogenesisand setting appropriate risk assessment parameters in humans.
Project 3820: Isolation and Purification of Mycotoxins from Fungi and Natural Compounds from Herbal Teas
Since the discovery of the major fumonisins, fumonisin B1, B2 and B3 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 continuously purified at the PROMEC Unit from maize cultures to be used as analytical standards both locally and abroad as well as for biological studies in various scientific fields. Many collaborative studies with local, other African and international centers have been conducted that resulted in scientific publications. The PROMEC unit continues to market and sell fumonisin standards to world renowned research centres. The sale of fumonisins has contributed more than R3 million to the PROMEC Unit budget over the past twelve years. Other mycotoxins isolated at PROMEC include TA-toxin from Alternaria alternata.
The role of nutraceuticals in the prevention of human diseases such as cancer is a relatively new and fast developing field of research. Research at the PROMEC Unit has shown that the unfermented aqueous extract of rooibos has a powerful protective effect against metabolically activated carcinogens in the Salmonella typhimurium mutagenicity test. Unfermented rooibos tea also exhibits potent antioxidant properties when considering its strong H-donating as well as O2 scavenging abilities. Although preliminary investigations indicate that this tea exhibits antimutagenic and antioxidant activity, very little is known about its constituents and their properties. These properties may be ascribed to the unique combination of polyphenols present in the tea. This study aims to isolate the active principles of rooibos tea by activity guided fractionation. These fractions will be characterized by HPLC and their components used in the formulation of flavonoid-rich concentrates that can be assessed for chemoprevention in vitro in cell culture and in vivo using a skin cancer rat model.
Project 3890: Modulation of the Cancer Initiating and Promotional Stages in Chemical Carcinogenesis
Fumonisin B1 (FB1), a natural occurring mycotoxin produced by the fungus Fusarium verticillioides in maize is known to disrupt cell membrane integrity and function. This mycotoxin causes several diseases in animals and is associated with a high incidence of human oesophageal and liver cancer in certain geographical areas in the world and the development of neural tube defects. FB1 is hepatotoxic and hepatocarcinogenic when chronically fed to rats, thus providing an excellent model to study the mechanisms associated with cancer induction by this non-genotoxic compound. FB1 lacks genotoxicity in Salmonella mutagenicity and DNA repair assays. However, it was recently reported that FB1 exhibited clastogenic properties. Short-term studies utilizing a cancer initiating/promoting model in rat liver indicated that FB1 closely mimics the characteristics of other genotoxic carcinogens with respect to initiation and promotion. With respect to cancer promotion, considerable evidence support a selection process whereby a few resistant hepatocytes proliferate in an environment where FB1 inhibited the growth of normal cells. FB1, therefore, acts in a manner similar to most cancer promoters by the induction of a growth differential, which selectively stimulates the outgrowth of initiated cells. FB1 was shown to be an inhibitor of the growth factor stimulatory response in primary hepatocytes in vitro and hepatocyte regeneration following partial hepatectomy in vivo. The disruption of lipid metabolism in the liver of rats at various levels involving sphingolipid, phospholipids, fatty acids and cholesterol appear to play an important role in this regard. At present little information is available regarding the effect of FB1 on lipid microdomains and the rate limiting enzyme in the cholesterol biosynthesis, HMG-CoA reductase. Of interest is the possible disruption of the insulin-metabolism due by FB1. Insulin receptors are known to be lodge in lipid microdomains.
Project 3900: Chemoprevention and Carcinogenesis: Role of Natural Dietary Components
Studies strongly support a tumour promoting role of inflammation in the development and progression of epithelial cancers. Antioxidants have the ability to prevent oxidant-induced damage due to their free radical scavenging and metal chelating functions in cells and thus have the ability to decrease the incidence of inflammation and therefore reduce the risk of SCC. Both rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) tea, two South African herbal teas, have been shown to contain a complex mixture of unique polyphenolic compounds that exhibit antioxidant and anti-inflammatory properties.
The inhibitory action of green and black tea (Camellia senensis) against experimental carcinogenesis has been demonstrated in many animal model systems including skin, liver, colon and oesophagus. These tea preparations inhibit carcinogenesis at initiation, promotion and progression stages. This project will investigate the effects of rooibos and honeybush herbal infusions on the development of cancer in in vivo carcinogenesis models. Potential anti-tumour mechanisms will include studies in in vitro cell cultures investigating the modulation of tumour growth (proliferation) and apoptosis.
Project 3995: Diet and Other Risk Factors Associated with Oesophageal Cancer in the Former Transkei
The Oesophageal Cancer (OC) incidence rates in the former Transkei region are amongst the highest in the world. In addition little is known about the current OC-associated risk factor patterns for people living in this high-risk area. The aim of the present study is to collect baseline information regarding dietary, nutritional and other OC-associated risk factors in a high-risk population living in different OC incidence areas.
Project 3996: The Modulating Role of Dietary Fatty Acids in the Development of Cancer
In vivo and in vitro studies have demonstrated the potential benefits of n-3 fatty acids (FA) in the prevention of colon cancer. It appears that the n-6/n-3 dietary FA ratio, rather than the quantity of n-3 FA, is the major determinant responsible for this chemopreventive effect. However, further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 FA intake on cancer prevention. Modulation of the altered lipid profile in cancerous tissue by dietary n-3 FA demonstrates the importance of changes to the membrane structure and function as well as the effect on cellular oxidative status in the regulation of cell growth. In this regard, modulation of arachidonic acid (AA, C20:4n-6) metabolism appears to be an important factor in carcinogenesis due to the influence on cell processes such as cellular proliferation and apoptosis. Metabolites from AA have been shown to influence signal transduction pathways that affect transcription factor activity and gene expression. Modulation of the oxidative status in cancer tissue by n-3 long-chain polyunsaturated FA (LCPUFA) also plays an important role in altering the growth of cancer cells. The primary objective of this study is to identify valid lipid biomarkers to assist in monitoring the effect of dietary FA as chemopreventive tools against colon cancer.
Investigations in an animal cancer model identified unique changes in lipid content and oxidative status in the liver of rats associated with the development of cancer. A similar lipid pattern was observed in liver cancer biopsies from human patients and certain lipid biomarkers were identified as possible endpoints for monitoring the altered growth pattern of cancer cells by dietary fatty acids. A subsequent modulation study in rats showed that the use of specific dietary ratios of n-6/n-3 fatty acids effectively reduced the growth of preneoplastic lesions in the liver, suggesting that changes in the liver tissue fatty acid profiles could be utilized as a chemopreventive tool in humans. Mechanisms relate to alterations in cell membrane lipid components and oxidative status. This hypothesis is currently being expanded to other organs, including the oesophagus and colon.
|
