PMID- 27757495
OWN - NLM
STAT- MEDLINE
DCOM- 20171218
LR  - 20171218
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 91
IP  - 5
DP  - 2017 May
TI  - Evaluation of the cytotoxic properties, gene expression profiles and secondary 
      signalling responses of cultured cells exposed to fumonisin B1, deoxynivalenol 
      and zearalenone mycotoxins.
PG  - 2265-2282
LID - 10.1007/s00204-016-1872-y [doi]
AB  - Mycotoxins are toxic secondary metabolites produced by a range of fungi and are 
      common contaminants of agricultural crops. These toxins are chemically diverse 
      and structurally stable, enabling them to enter the food chain which can lead to 
      numerous adverse health effects in animals and humans. Although mycotoxin 
      exposure is associated with the development of several cancers, it has proved 
      challenging to show a direct connection between exposure and oncogenic change. 
      This study investigates the in vitro cytotoxicity, molecular mechanisms and 
      secondary signalling responses associated with the exposure to three major 
      mycotoxins, fumonisin B1 (FB1), deoxynivalenol (Don) and zearalenone (Zea). The 
      cytotoxicity of FB1, Don and Zea were investigated in cultured HepG2 and Caco-2 
      cells using cell viability assays as well as flow cytometry. FB1 proved to be 
      less cytotoxic than its counterparts, while Don and Zea demonstrated high 
      cytotoxicity through an apoptotic mechanism. Expression profiles of 84 genes 
      involved in mediating communication between tumour cells and the cellular 
      mediators of inflammation as well as the innate immune system were also studied. 
      The expression profiles associated with the different mycotoxins were further 
      explored for functional networks, biological functions, canonical pathways, 
      toxicological association as well as to predict network associations between the 
      differentially expressed genes. RT-qPCR revealed the significant differential 
      expression of 46 genes, including the expression of several genes strongly 
      associated with cancer and aberrant inflammatory signalling, after mycotoxin 
      exposure. Aberrant inflammatory signalling seems to be a credible contributing 
      factor that initiates the malignant change observed in cells exposed to 
      mycotoxins.
FAU - Wentzel, Johannes F
AU  - Wentzel JF
AD  - Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West 
      University, Potchefstroom, 2520, South Africa. wentzel.jf@gmail.com.
FAU - Lombard, Martani J
AU  - Lombard MJ
AD  - Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, 
      2520, South Africa.
FAU - Du Plessis, Lissinda H
AU  - Du Plessis LH
AD  - Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West 
      University, Potchefstroom, 2520, South Africa.
FAU - Zandberg, Lizelle
AU  - Zandberg L
AD  - Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom, 
      2520, South Africa.
LA  - eng
PT  - Journal Article
DEP - 20161018
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Fumonisins)
RN  - 0 (Mycotoxins)
RN  - 0 (Trichothecenes)
RN  - 3ZZM97XZ32 (fumonisin B1)
RN  - 5W827M159J (Zearalenone)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
RN  - JT37HYP23V (deoxynivalenol)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Caco-2 Cells
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - Computer Simulation
MH  - Flow Cytometry/methods
MH  - Fumonisins/*toxicity
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Mycotoxins/toxicity
MH  - Signal Transduction/drug effects
MH  - Trichothecenes/*toxicity
MH  - Zearalenone/*toxicity
OTO - NOTNLM
OT  - Deoxynivalenol (Don)
OT  - Fumonisin B1 (FB1)
OT  - Gene expression profiling
OT  - Mycotoxins
OT  - Secondary signalling responses
OT  - Zearalenone (Zea)
EDAT- 2016/10/21 06:00
MHDA- 2017/12/19 06:00
CRDT- 2016/10/21 06:00
PHST- 2016/06/22 00:00 [received]
PHST- 2016/10/06 00:00 [accepted]
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2016/10/21 06:00 [entrez]
AID - 10.1007/s00204-016-1872-y [pii]
AID - 10.1007/s00204-016-1872-y [doi]
PST - ppublish
SO  - Arch Toxicol. 2017 May;91(5):2265-2282. doi: 10.1007/s00204-016-1872-y. Epub 2016 
      Oct 18.