Tygerberg, South Africa
Tygerberg, South Africa

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Van Der Westhuizen L.,PROMEC Unit | Shephard G.S.,PROMEC Unit | Burger H.M.,PROMEC Unit | Burger H.M.,Stellenbosch University | And 5 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2011

Background: The consumption of maize highly contaminated with carcinogenic fumonisins has been linked to high oesophageal cancer rates. The aim of this study was to validate a urinary fumonisin B1 (UFB1) biomarker as a measure of fumonisin exposure and to investigate the reduction in exposure following a simple and culturally acceptable intervention. Methods: At baseline home-grown maize, maize-based porridge, and first-void urine samples were collected from female participants (n = 22), following their traditional food practices in Centane, South Africa. During intervention the participants were trained to recognize and remove visibly infected kernels, and to wash the remaining kernels. Participants consumed the porridge prepared from the sorted and washed maize on each day of the two-day intervention. Porridge, maize, and urine samples were collected for FB1 analyses. Results: The geometric mean (95% confidence interval) for FB1 exposure based on porridge (dry weight) consumption at baseline and following intervention was 4.84 (2.87-8.14) and 1.87 (1.40-2.51) μg FB1/kg body weight/day, respectively, (62% reduction, P < 0.05). UFB1C, UFB1 normalized for creatinine, was reduced from 470 (295-750) at baseline to 279 (202-386) pg/mg creatinine following intervention (41% reduction, P = 0.06). The UFB 1C biomarker was positively correlated with FB1 intake at the individual level (r = 0.4972, P < 0.01). Urinary excretion of FB1 was estimated to be 0.075% (0.054%-0.104%) of the FB1 intake. Conclusion: UFB1 reflects individual FB1 exposure and thus represents a valuable biomarker for future fumonisin risk assessment. Impact: The simple intervention method, hand sorting and washing, could positively impact on food safety and health in communities exposed to fumonisins. ©2011 AACR.


Somdyala N.I.,Burden of Disease Research Unit | Bradshaw D.,Burden of Disease Research Unit | Gelderblom W.C.,PROMEC Unit | Gelderblom W.C.,Stellenbosch University | Parkin D.M.,University of Oxford
International Journal of Cancer | Year: 2010

Cancer incidence rates and patterns are reported for a rural population, living in the Eastern Cape Province of South Africa for the period 1998-2002. The population-based cancer registry has operated for 20 years, using both active and passive methods for case finding, through collaborations with 19 health facilities: 11 district hospitals, 7 referral hospitals and 1 regional laboratory. The age standardized incidence rates for all cancers were 73.1 per 100,000 in males and 64.1 per 100,000 in females. The leading top 5 cancers for males were oesophagus (32.7 per 100,000), lung (5.8 per 100,000), prostate (4.4 per 100,000), liver (4.4 per 100,000) and larynx (2.5 per 100,000) whereas for females they were cervix (21.7 per 100,000), oesophagus (20.2 per 100,000), breast (7.5 per 100,000), ovary (0.9 per 100,000) and liver (0.9 per 100,000). The incidence of Kaposi sarcoma was low, and higher for males (1.6 per 100,000) than females (0.3 per 100,000). Lung cancer in both males and females was relatively low compared to the high incidence of oesophagus cancer. © 2010 UICC.


Van Der Westhuizen L.,PROMEC Unit | Shephard G.S.,PROMEC Unit | Gelderblom W.C.A.,PROMEC Unit | Gelderblom W.C.A.,Stellenbosch University | Riley R.T.,U.S. Department of Agriculture
World Mycotoxin Journal | Year: 2013

Maize is the predominant food source contaminated by fumonisins and this has particular health risks for communities consuming maize as a staple diet. The main biochemical effect of fumonisins is the inhibition of ceramide biosynthesis causing an increase in sphingoid bases and sphingoid base 1-phosphates and a depletion of the complex sphingolipids, thereby disrupting lipid metabolism and sphingolipid-mediated processes and signalling systems. Attempts to use the elevation of sphinganine as a human biomarker of fumonisin exposure have to date been unsuccessful. Consequently, recent research has focussed on developing a urinary exposure biomarker based on the measurement of the nonmetabolised toxin. In animals, fumonisins are poorly absorbed in the gut and are mostly excreted unmetabolised in faeces, with only a small percentage (0.25-2.0%) in urine. This appears to also be true in humans were fumonisin B1 (FB1) is detectable in urine soon after exposure, but in very small amounts relative to total intake. However, with modern sensitive and selective analytical methods such as liquid chromatography-tandem mass spectrometry, these low levels can be readily determined. The first study to show a positive correlation between consumption of maize and urinary FB 1 was conducted in a Mexican population consuming tortillas as a staple food. Further validation of this relationship was achieved in a South African subsistence farming community with a positive correlation between urinary FB1 and fumonisin exposure, as assessed by food analysis and food intake data. The most recent developments are aimed at measuring multiple mycotoxin biomarkers in urine, including FB1. Current exposure studies in Guatemala are combining the urinary biomarker with measurement of sphinganine-1-phosphate in blood spots as a measure of biochemical effect. Thus, the urinary FB1 biomarker could contribute considerably in assessing the adverse health impact of fumonisin exposure.


Gelderblom W.C.A.,PROMEC Unit | Gelderblom W.C.A.,Stellenbosch University | Marasas W.F.O.,PROMEC Unit | Marasas W.F.O.,Stellenbosch University
Human and Experimental Toxicology | Year: 2012

Fusarium verticillioides causes several animal diseases and the contamination maize suggests that it could adversely affect human health. The fumonisin B mycotoxins were characterized from the fungal culture material and shown to be the causative principle responsible for the major mycotoxicological effects of the fungus in experimental and farm animals. The main focus was on the toxicological effects in rats and mice, the outcome of which played an important role in setting risk assessment parameters for exposure of the fumonisins to humans. The International Agency for Research on Cancer characterized the fumonisins as Group 2B carcinogens. Several controversial findings regarding the toxicological effects of the culture material of the fungus, the genotoxicity and carcinogenicity of pure fumonisin B1 (FB1) in rats have been reported that should be clarified prior to assessing the risk in humans. The underlying differences between the diets with the high protein levels are likely to sensitize the kidneys to FB1-induced toxic and carcinogenic effects. Several other dietary factors, such as plant extracts (antioxidants) and dietary Fe, could either stimulate or inhibit cancer induction of FB1, which complicates the comparison of toxicological effects in experimental animals. Cognisance should be taken of the modulating role of dietary constituents as it will determine the outcome of toxicological assays and determine the threshold of an adverse effect in a specific target organ to be used in determining risk assessment parameters. © SAGE Publications 2012.


Schloms L.,Stellenbosch University | Storbeck K.-H.,Stellenbosch University | Swart P.,Stellenbosch University | Gelderblom W.C.A.,Stellenbosch University | And 2 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2012

The steroid hormone output of the adrenal gland is crucial in the maintenance of hormonal homeostasis, with hormonal imbalances being associated with numerous clinical conditions which include, amongst others, hypertension, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes. Aspalathus linearis (Rooibos), which has been reported to aid stress-related symptoms linked to metabolic diseases, contains a wide spectrum of bioactive phenolic compounds of which aspalathin is unique. In this study the inhibitory effects of Rooibos and the dihydrochalcones, aspalathin and nothofagin, were investigated on adrenal steroidogenesis. The activities of both cytochrome P450 17α-hydroxylase/17,20 lyase and cytochrome P450 21-hydroxylase were significantly inhibited in COS-1 cells. In order to study the effect of these compounds in H295R cells, a human adrenal carcinoma cell line, a novel UPLC-MS/MS method was developed for the detection and quantification of twenty-one steroid metabolites using a single chromatographic separation. Under both basal and forskolin-stimulated conditions, the total amount of steroids produced in H295R cells significantly decreased in the presence of Rooibos, aspalathin and nothofagin. Under stimulated conditions, Rooibos decreased the total steroid output 4-fold and resulted in a significant reduction of aldosterone and cortisol precursors. Dehydroepiandrosterone-sulfate levels were unchanged, while the levels of androstenedione (A4) and 11β-hydroxyandrostenedione (11βOH-A4) were inhibited 5.5 and 2.3-fold, respectively. Quantification of 11βOH-A4 showed this metabolite to be a major product of steroidogenesis in H295R cells and we confirm, for the first time, that this steroid metabolite is the product of the hydroxylation of A4 by human cytochrome P450 11β-hydroxylase. Taken together our results demonstrate that Rooibos, aspalathin and nothofagin influence steroid hormone biosynthesis and the flux through the mineralocorticoid, glucocorticoid and androgen pathways, thus possibly contributing to the alleviation of negative effects arising from elevated glucocorticoid levels. © 2011 Elsevier Ltd. All rights reserved.


Shephard G.S.,PROMEC Unit | van der Westhuizen L.,PROMEC Unit | Sewram V.,Oncology Research Unit | van Zyl J.,Indigenous | Rheeder J.P.,PROMEC Unit
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

Fumonisins are a group of structurally related mycotoxins produced mainly in maize by Fusarium verticillioides and F. proliferatum. The most abundant naturally occurring analogue is fumonisin B 1 (FB 1), with lesser amounts of fumonisin B 2 (FB 2) and fumonisin B 3 (FB 3) occurring. The C-series fumonisins (FCs) are structurally analogous to the B-series but lack the C-1 methyl group. Good and mouldy subsistence-grown maize samples were collected from the Centane and Bizana districts in the former Transkei region of South Africa. After extraction with methanol/water and clean-up on strong anion exchange solid phase extraction cartridges, FB 1, FB 2, FB 3, FC 1, FC 3 and FC 4 were determined by reversed-phase LC-MS/MS using positive ion electrospray ionisation. FB 1 levels in both good and mouldy maize from Centane (means (±SD) 2.75 ± 2.24 and 23.4 ± 12.5 mg kg -1, respectively) were higher than the corresponding levels in maize samples from Bizana (means 0.056 ± 0.157 and 3.71 ± 5.01 mg kg -1, respectively). Similarly, FC 1 levels in both good and mouldy maize from Centane (means 0.107 ± 0.099 and 0.814 ± 0.391 mg kg -1, respectively) were higher than in Bizana, where FC 1 was detected in only one (0.018 mg kg -1) of 19 good maize samples and occurred in mouldy maize with a mean of 0.102 ± 0.135 mg kg -1. A significant correlation (r = 0.982, p < 0.01) was observed between FB 1 and FC 1 levels in all samples, with FC 1 levels at 3.3% of the corresponding FB 1 levels. FC 4 levels were similar to FC 1, whereas only low amounts of FC 3 were detected. © 2011 Copyright Taylor and Francis Group, LLC.


Ghiasian S.A.,Hamadan University of Medical Sciences | Ghiasian S.A.,Tehran University of Medical Sciences | Shephard G.S.,PROMEC Unit | Yazdanpanah H.,Tehran University of Medical Sciences
Mycopathologia | Year: 2011

Fifty-one maize samples, intended for animal feed and human consumption, were collected from the four main maize production provinces in Iran and analyzed by high-performance liquid chromatography (HPLC) for contamination by four naturally occurring aflatoxin analogues (AFB1, AFB2, AFG1, and AFG2). AFB1 was detected in 58.3, and 80% of the maize samples obtained from Kermanshah and Mazandaran provinces, respectively. The maximum AFB1 (276.3 μg/kg) and highest level of total aflatoxins (AFT) (316.9 μg/kg) were detected in a maize sample collected from Kermanshah province. The mean aflatoxin level from contaminated samples (52.60 μg/kg) from Kermanshah was significantly higher (P < 0.0001) than those in maize from the other three provinces and exceeded all the maximum tolerated levels (MTLs) set for AFT in maize. The level of AFB1 in 15.68% of the total samples was above the MTL (5 μg/kg) for AFB1 in maize in Iran. The mean contamination level of AFT (23.86 μg/kg) in the positive samples was higher than MTL for maize in Iran (20 μg/kg) intended for animal feed. The levels of AFB1, AFB2, AFG1, and AFG2 ranged between not detected (<0.1 μg/kg) and 276.3, 30.4, 9.1, and 1.1 μg/kg in maize grain, respectively. © 2011 Springer Science+Business Media B.V.


Ndube N.,PROMEC Unit | van der Westhuizen L.,PROMEC Unit | Green I.R.,University of the Western Cape | Shephard G.S.,PROMEC Unit
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2011

Fumonisins are mycotoxins produced by various species of Fusarium and occur naturally in contaminated maize and maize-based foods. Ingestion of fumonisins has considerable health implications for humans and animals. Since fumonisins lack a useful chromophore or fluorophore, their determination in maize is routinely achieved via HPLC with fluorescence detection (FLD) after precolumn derivatization. This study optimized naphthalene-2,3-dicarboxaldehyde (NDA) derivatization of fumonisins in naturally contaminated maize following strong anion exchange (SAX) solid phase extraction (SPE) clean-up and utilizing diode array detection (DAD) as a practical alternative simultaneously to FLD. The limit of detection (LOD) for fumonisin B 1 (FB 1), fumonisin B 2 (FB 2) and fumonisin B 3 (FB 3) with FLD was 0.11ng, 0.50ng and 0.27ng, respectively, and with DAD it was 13.8ng, 12.5ng and 6.6ng, respectively injected on column. The coefficient of variation (CV, n=6) for FB 1, FB 2 and FB 3 in a naturally contaminated samples obtained with FLD was 2.6%, 1.8% and 5.3%, respectively, compared to 6.0%, 3.4% and 9.5%, respectively, obtained with DAD. Subsequently the optimized NDA derivatization was compared to the widely used o-phthaldialdehyde (OPA) derivatization agent as well as alternative sample clean-up with immunoaffinity column (IAC) by analyzing naturally contaminated maize samples (n=15) ranging in total fumonisin (TFB=FB 1+FB 2+FB 3) levels from 106 to 6000μg/kg. After immunoaffinity column clean-up of extracted samples, the recoveries of spiked maize samples for NDA-FLD of FB 1, FB 2 and FB 3 were 62%, 94% and 64%, respectively. NDA proved to be an effective derivatization reagent of fumonisin in naturally contaminated maize samples following IAC clean-up, except for DAD at TFB levels below 1000μg/kg. In contrast NDA derivatization following SAX clean-up produced results comparable to OPA only for levels below 1000μg/kg. Aside from the difference in detection limits, FLD and DAD produced comparable results irrespective of the clean-up method or the derivatization agent. © 2011 Elsevier B.V.


Khlangwiset P.,University of Pittsburgh | Shephard G.S.,PROMEC Unit | Wu F.,University of Pittsburgh
Critical Reviews in Toxicology | Year: 2011

Aflatoxins, fungal toxins produced by Aspergillus flavus and Aspergillus parasiticus in a variety of food crops, are well known as potent human hepatocarcinogens. Relatively less highlighted in the literature is the association between aflatoxin and growth impairment in children. Foodborne aflatoxin exposure, especially through maize and groundnuts, is common in much of Africa and Asiaareas where childhood stunting and underweight are also common, due to a variety of possibly interacting factors such as enteric diseases, socioeconomic status, and suboptimal nutrition. The effects of aflatoxin on growth impairment in animals and human children are reviewed, including studies that assess aflatoxin exposure in utero and through breastfeeding. Childhood weaning diets in various regions of the world are briefly discussed. This review suggests that aflatoxin exposure and its association with growth impairment in children could contribute a significant public health burden in less developed countries. © 2011 Informa Healthcare USA, Inc.


van der Westhuizen L.,PROMEC Unit | Shephard G.S.,PROMEC Unit | Rheeder J.P.,PROMEC Unit | Burger H.-M.,PROMEC Unit
Food and Chemical Toxicology | Year: 2010

Low and high oesophageal cancer incidence areas of the former Transkei region of South Africa have been associated with corresponding low and high levels of fumonisin contaminated home-grown maize. This is the first study in South Africa assessing fumonisin B (FB) mycotoxin exposure by quantifying individual maize consumption with weighed food records and FB levels from maize in each participant's household and concurrently evaluating sphinganine (Sa), sphingosine (So) and Sa/So ratios in plasma and urine of these participants as possible biomarkers of FB exposure. The high consumption of maize in Bizana (n=36) and Centane (n=30) of 0.41±0.21 and 0.39±0.19kg/day, respectively, confirms the reliance on maize as the dietary staple. Mean total FB (FB1+FB2+FB3) levels in home-grown maize were 0.495+0.880 and 0.665+0.660mg/kg in Bizana and Centane, respectively. Mean fumonisin exposure based on individual consumption was 3.9±7.3 and 4.1±7.6μg/kg body weight/day, respectively, for Bizana and Centane. The mean combined sphinganine/sphingosine ratios in Bizana and Centane were similar and ranged from 0.10-0.55 in plasma (n=41) and urine (n=62). There was no association between sphingoid base levels and/or Sa/So ratios in the plasma and urine and individual fumonisin exposure, negating the sphingoid bases as potential biomarkers of fumonisin exposure in humans. © 2010 Elsevier Ltd.

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