Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Exposure to food contaminates such as mycotoxins have been associated with a
variety of animal and human diseases worldwide. In South Africa, maize is the most To further refine risk assessment in the socio-demographic heterogeneous
population of South Africa, the development and evaluation of a sensitive and
interactive model the Mycotoxin Risk Assessment Model (MYCORAM) proofed to be
more sensitive compared to the classical probable daily intake (PDI). The
development of the MYCORAM was based on mycotoxin distribution during dry
milling of maize in milling fractions intended for human consumption which was
superimposed on the maize intake profiles of the South African population. Although
dry milling, including a degerming step, is an effective way to reduce mycotoxins, risk
and exposure assessment are influenced by maize dietary intakes, gender and
ethnicity. This became evident when considering FB dietary exposure in rural maize
subsistence farming communities in the Eastern Cape Province, South Africa
confirmed the vulnerability of this subpopulation to risk of fumonisin exposure.
Specific maximum tolerated maximum levels (MTL) to safeguard these communities
fall outside the international regulatory processes and need to be urgently
addressed. With the complex nature of cancer development in mind, integration of
basic science and nutritional epidemiology will be important to contribute to our
understanding of the adverse effects of FB and to define relevant risk assessment
parameters.
important commercial grain crop not just economically but also as a local food
commodity both commercially and in subsistence rural farming communities. In order
to control and manage mycotoxin contamination in food, evidence-based risk
assessment is needed that includes mechanistic and human exposure studies. From
this perspective the current study was conducted and aimed in further unravelling
fumonisin B1 (FB1) mycotoxin induced hepatocarcinogenesis via the disruption of the
lipid metabolism. The study also critically evaluates aspects of human risk
assessment due to its relevance and importance to food safety known to impact on
food security. This entails mycotoxin distribution during maize dry milling and the
assessment of mycotoxin exposure in the South African population and vulnerable
rural communities at risk.
Fumonisin B1 affects the integrity of biological membranes by altering key lipid and
fatty acid parameter in plasma, microsomal, mitochondrial and nuclear subcellular
membrane fractions in rat liver. Changes in the major lipid constituents entailing an
increase in cholesterol (CHOL) and phosphatidylethanolamine (PE) whilst
sphingomyelin (SM) and phosphatidylcholine (PC) tended to decrease. Isolated
plasma membrane lipid rafts, from rat primary hepatocytes exposed to FB1
augments the intricate effects exerted on the lipid metabolism regarding CHOL, SM
and PE. The disruption of lipid and fatty acid constituents, such as arachidonic acid
and ceramide, are likely to be key determinants affecting growth regulatory signaling
pathways relevant to the critical balance between cell proliferation and apoptosis
during cancer promotion. These changes provide further evidence that FB1 induce
cancer promotion by differential inhibition and/or stimulation process whereby a few
resistant “initiated” hepatocytes proliferate in an environment where the growth of
normal cells is inhibited. A specific lipogenic phenotype is effected by FB1 which is
closely associated with cancer development and considered to occur via an
epigenetic-type of mechanism. These effects are not adequately addressed in
defining risk assessment parameters. / AFRIKAANSE OPSOMMING: Die blootstelling aan voedsel-kontaminante soos mikotoksienes word wêreldwyd met
‘n verskeidenheid van dierlike en menslike siektes geassosiseer. In Suid-Afrika word
mielies as ‘n belangrike graanoes beskou, nie net vir die ekonomie nie maar ook as
‘n plaaslike voedselproduk beide kommersieel en vir bestaansboere in landelike
gemeenskappe. Ten einde mikotoksien-kontaminasie van voedsel te kan beheer en
bestuur, vereis bewys-gebaseerde risiko-evaluering wat insluit meganistiese en
menslike blootstelling studies. Vanuit hierdie perspektief is die huidige studie
uitgevoer en gemik op die verdere ontleding van die fumonisin B1 (FB1) mikotoksien
geïnduseerde lewer-karsinogenese deur die ontwrigting van die lipiedmetabolisme.
Die studie ondersoek terselfdetyd aspekte van menslike risiko-evaluering ingevolge
die relevansie en belangrikheid hiervan in voedselveiligheid wat ook ‘n impak op
voedselsekerheid sal maak. Dit sluit in die verspreiding van mikotoksiene gedurende
die droëmaalproses van mielies en mikotoksien blootstelling in Suid-Afrika asook
onder kwesbare landelike gemeenskappe. Fumonisin B1 beïnvloed die integriteit van biologiese membrane deur die modulasie
van die belangrike lipied en vetsuur samestelling van plasma, mikrosomale,
mitochondriale en kern subsellulêre membraan-fraksies in rot lewer. Veranderinge in
die belangrike lipiedbestanddele, insluitende ‘n verhoging in cholesterol (CHOL) en
phosphatidylethanolamine (PE), terwyl sphingomyelin (SM) en phosphatidylcholine
(PC) geneig was om te verlaag. Geïsoleerde plasma membraan lipied vlotte (lipid
rafts), vanaf primêre rot hepatosiete blootgestel aan FB1, versterk die ingewikkelde
gevolge wat uitgeoefen word op die lipiedmetabolisme insluitende die voorgestelde
veranderings in CHOL, SM en PE vlakke. Die versteuring van lipiede en vetsure
soos aragidoonsuur (arachidonic acid) en ceramied kan beskou word as belangrike
determinante wat inmeng in groei-regulerende seinbane verwant aan die kritiese
balans tussen selgroei en seldood. Die versteurings verskaf verdere bewyse dat FB1
kanker bevorder deur ‘n seleksie proses wat onderskeidelike die onderdrukking en\of
die stimulasie van ‘n paar weerstandige of geneties veranderde hepatosiete laat
vermeerder in ‘n omgewing waar die groei van normale selle geïnhibeer word. Die
spesifieke lipogeniese fenotipe wat FB1 versoorsaak hou ten nouste verband met kankerontwikkeling en die voorkoms van epigenetiese-soort meganismes word
voorgestel. Hierdie oorsake word tans nie voldoende aangespreek tydens die
bepaling van risiko-evaluerings limiete nie.
Om risiko-bepaling verder te verbeter in die sosio-demografies heterogene populasie
van Suid-Afrika, was die ontwikkeling en evalueering van ‘n sensitiewe en
interaktiewe model, die “Mycotoxin Risk Assessment Model” (MYCORAM) meer
doeltreffend vergeleke met die gewone waarskynlike daaglikse inname. Die
ontwikkeling van die MYCORAM was gebaseer op die mikotoksien verspreiding
tydens die droëmaalproses van mielies in fraksies wat vir menslike verbruik bedoel
was tesame met mielie dieetinnames van die Suid-Afrikaanse populasie. Alhoewel,
die droëmaalproses van mielies, insluitende die verwydering van die kiem
doeltreffende maniere is om mikotoksienes te verminder, word risiko- en
blootstellings evaluering beinvloed deur mielie dieetinnames, geslag en etnieseverbandskap.
Hierdie was veral opmerklik gedurende blootstelling aan FB in die
dieet van landelike mielie bestaansboer gemeenskappe in die Oos-Kaap van Suid-
Afrika en bevestig hoe kwesbaar hierdie populasie is. Spesifieke maksimum
toelaatbare vlakke om hierdie gemeenskappe te beskerm val buite die huidige
internasionale regulatoriese prosesse en benodig dringende aandag. Met die
ingewikkelde aard van kankerontwikkeling in gedagte, sal die integrasie van basiese
wetenskappe en voedingsepidemiologie, ‘n belangrik bydrae lewer tot die kennis van
die negatiewe eienskappe van FB om toepaslike risiko-evaluerings limiete te kan
bepaal.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/85610 |
| Date | 12 1900 |
| Creators | Burger, Hester Maria |
| Contributors | Gelderblom, W. C. A., Swart, P., Stellenbosch University. Faculty of Science. Dept. of Biochemistry. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | xxiii, 278 p. : col. ill. |
| Rights | Stellenbosch University |
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