Evaluation of the cytotoxic properties, gene expression profiles and secondary signalling responses of cultured cells exposed to fumonisin B1, deoxynivalenol and zearalenone mycotoxins
| Autor: | Johannes F. Wentzel, Martani J Lombard, Lizelle Zandberg, Lissinda H. Du Plessis |
|---|---|
| Přispěvatelé: | 20134045 - Wentzel, Johannes Frederik, 25719815 - Lombard, Martani Johanni, 11948388 - Du Plessis, Lissinda Hester, 12257656 - Zandberg, Lizelle |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Apoptosis Biology Toxicology Fumonisins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression Humans Computer Simulation Secondary signalling responses Viability assay Deoxynivalenol (Don) Mycotoxin Cytotoxicity Zearalenone (Zea) Caspase 7 Regulation of gene expression Fumonisin B1 Innate immune system L-Lactate Dehydrogenase Caspase 3 business.industry Gene Expression Profiling Fumonisin B1 (FB1) food and beverages Hep G2 Cells General Medicine Mycotoxins Flow Cytometry Gene expression profiling Biotechnology Cell biology 030104 developmental biology Gene Expression Regulation chemistry 030220 oncology & carcinogenesis Zearalenone Caco-2 Cells Trichothecenes business Signal Transduction |
| Zdroj: | Archives of Toxicology. 91:2265-2282 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-016-1872-y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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