Fumonisin exposure biomarkers in humans consuming maize staple diets

Van der Westhuizen, Liana (Stellenbosch : University of Stellenbosch, 2011-03)

Thesis (PhD (MedSc))--University of Stellenbosch, 2011.

Thesis

ENGLISH ABSTRACT: Fumonisins are carcinogenic mycotoxins which occur world-wide in maize and maize-based products intended for human consumption. Consumption of fumonisin contaminated maize as a staple diet has been associated with oesophageal and liver cancer incidence as well as neural tube defects. This study has confirmed the State of Santa Catarina, Brazil as another region where the consumption of maize contaminated with fumonisins and high oesophageal cancer incidence co-occur. Since fumonisins exert their main biochemical effect by disruption of the sphingolipid biosynthetic pathway and are implicated in cancer, the role of fumonisin B1 (FB1) in FB1–induced rat hepatocyte nodules was investigated. The current study showed that FB1 exposure activated sphingosine accumulation in the nodules which could induce the bio-active sphingosine 1-phosphate to provide a selective growth stimulus on subsequent FB1 exposure. Since the FB1-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, it was not the mechanism whereby the altered hepatocytes escaped the mitoinhibition of FB1 and selectively proliferated into hepatocyte nodules. A study in maize subsistence farming communities investigated the sphingosine and sphinganine levels in blood and urine of participants. Fumonisin exposure was assessed in these communities based on fumonisin levels in maize that was concurrently collected from the areas where the participants resided. Subsequently fumonisin exposure was assessed in individuals based on the fumonisin levels in maize collected from each household and by acquiring weighed food records for each member of the household. It was confirmed in both these studies that communities are chronically exposed to fumonisin levels well above the provisional maximum tolerable daily intake determined by the Joint FAO/WHO Expert Committee on Food Additives. Since the sphinganine and sphingosine levels in blood and urine of the participants exposed to various levels of fumonisin were not significantly different, the sphingoid bases and their ratios could not be established as a biomarker of fumonisin exposure. Therefore, an alternative biomarker of exposure was investigated during studies into a practical cost effective method to reduce fumonisin. The customary maize food preparation practices were assessed in a maize subsistence farming community and subsequently optimised to reduce the fumonisin levels in the maize under laboratory-controlled conditions. Implementation of this optimised and culturally acceptable intervention method of sorting and washing maize in a rural community reduced fumonisin contamination in home-grown maize by 84%. The intervention study attained a 62% reduction in fumonisin exposure based on fumonisin levels in maize-based food and consumption as assessed by 24-h dietary recall questionnaires. The alternative biomarker of fumonisin exposure, urinary FB1, was investigated during the intervention study. The FB1 urinary biomarker measured fumonisin intake at the individual level and confirmed the reduction achieved as assessed by food analysis and food intake data. The biomarker was thus well correlated with fumonisin exposure and confirmed the efficacy of the simple and culturally acceptable intervention method. Utilisation of the urinary FB1 biomarker and the customised hand-sorting and washing of maize to reduce fumonisin exposures has the potential to improve food safety and health in subsistence maize farming communities.

AFRIKAANSE OPSOMMING: Fumonisien is kankerverwekkende mikotoksiene wat wêreldwyd voorkom op mielies en mielie-verwante produkte bestem vir menslike verbruik. Daar is ‘n verband tussen die voorkoms van slukderm en lewer kanker, sowel as neuraalbuisdefekte, in gemeenskappe waar fumonisien-gekontamineerde mielies die stapel voedsel is. Die Brasiliaanse Staat, Santa Catarina is uitgewys as nog 'n area waar hoë voorkoms van slukdermkanker en hoë fumonisin vlakke in mielies gesamentlik voorkom. Aangesien fumonisien verbind word met van kanker en die hoof biochemiese effek die ontwrigting van die sfingolipiedbiosintese weg is, is die rol van fumonisien B1 (FB1) in FB1-geinduseerde rot hepatosietnodules ondersoek. Die studie het getoon dat FB1 blootstelling aktiveer sfingosien ophoping in die hepatosietnodules wat moontlik die bio-aktiewe sfingosien 1-fosfaat aktiveer om op daaropvolgende FB1 blootstellings geselekteerde groei stimulasie te ondergaan. Die FB1-geïnduseerde hepatosietnodules was nie bestand teen die inhibisie van die sfingolipied biosintese nie en dus nie die meganisme waardeur die veranderde hepatosiete mito- inhibisie van FB1 vryspring, en selektief ontwikkel in hepatosietnodules nie. ‘n Studie in bestaansboerdery gemeenskappe het die sfingosien en sfinganien vlakke in bloed en uriene vergelyk met individuele fumonisien blootstelling. Laasgenoemde is gebaseer op fumonisien vlakke in gekolleekterde mielies vanuit die deelnemers se huise en aannames vanuit die literatuur. Die opvolg studie in die areas het individuele fumonisien blootstelling bepaal gebaseer op fumonisien vlakke in die mielies van elke huishouding en die inname van mielies deur die voedsel van elke individu te weeg. Albei hierdie studies het bevestig dat die gemeenskappe blootgestel is aan kroniese fumonisien vlakke wat die maksimum toelaatbare daaglikse inname wat deur die gesamentlike FAO/WHO deskundige komitee op voedsel toevoegsels vasgestel is, oorskei. Aangesien die sfingosien en sfinganien vlakke nie beduidend verskil in bloed of uriene van mense wat aan verskillende fumonisien-kontaminasie vlakke blootgestel is nie, kan die lipiedbasisse en hul verhouding nie as ‘n biologiese merker vir fumonisien blootstelling bevestig word nie. Dus is ‘n alternatiewe biologiese merker vir fumonisien blootstelling ondersoek gedurende ‘n studie oor praktiese bekostigbare maniere om fumonisin blootstelling te verlaag. Die tradisionele voedsel voorbereidingspraktyke in ‘n bestaansboerdery gemeenskap is bestudeer en onder laboratorium-gekontroleerde toestande aangepas om fumonisien vlakke in die mielies optimaal te verlaag. Die kultureel aanvaarbare intervensie metode, sortering en was van die mielies, is in ‘n bestaansboerdery gemeenskap toegepas waar ‘n 84% verlaging in fumonisien vlakke van die mielies verkry is. Die intervensie metode het ‘n 62% verlaging in fumonisien blootstelling te weeggebring deur fumonisien vlakke in die mieliegebasserde disse te meet en inname daarvan deur die deelnemers met 24-h diëetkundige vraelyste vas t e stel. Gedurende die intervensie studie is urienêre FB1, die alternatiwe biologiese merker van fumonisien blootstelling, ondersoek. Individuele fumonisien blootstelling data, bepaal met die urienêre FB1 biomerker, het goed ooreengestem met die voedsel analise en voedsel inname data en het dus die doeltreffendheid van die praktiese kultuur aanvaarbare intervensie metode bevestig. Benutting van die FB1 urienêre biologies merker en die optimale sortering en was van die mielies om die fumonisien blootstelling te verlaag het die potensiaal om voedselveiligheid en gesondheid in hierdie bestaansboerdery gemeenskappe aansienlik te verbeter.

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