Mycotoxins and Human Carcinogenesis: Exploring Causal Links by Exposure Assessment and Poly-Omics Designs.

Promovendus/a
Claeys, Liesel
Faculteit
Faculteit Farmaceutische Wetenschappen
Vakgroep
Vakgroep Bioanalyse
Curriculum
Master of Sciences in Drug Development, magna cum laude, Ghent University, Belgium, 2018; Bachelor in Pharmaceutical Sciences, cum laude, Ghent University, Belgium, 2016; Science – Mathematics, cum laude, Examencommissie, Brussels, Belgium, 2013.
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Engels
Vertaling titel
Mycotoxinen en Humane Carcinogenese: het Verkennen van Causale Verbanden door Blootstellingsevaluatie en Poly-omics Designs.
Promotor(en)
Prof. dr. Sarah De Saeger, UGent-Bioanalyse - Prof. dr. Marthe De Boevre, UGent-Bioanalyse - Dr. Inge Huybrechts, International Agency for Research on Cancer, Nutrition and Metabolism Branch
Examencommissie
Prof. dr. Lies Lahousse, UGent-Bioanalyse - Prof. dr. Dieter Deforce, UGent-Geneesmiddelenleer - Prof. Dr. Jana Asselman, UGent-Faculty of Bioscience Engineering - Prof. Dr. Liesbeth Jacxsens, UGent-Faculty of Bioscience Engineering - Dr. Zdenko Herceg, International Agency for Research on Cancer, Epigenomics and Mechanisms Branch - Dr. Emmanuel Tangni, Sciensano

Korte beschrijving

Mycotoxins are toxic secondary metabolites that are naturally produced by different fungi. Recent reports revealed that 60% to 80% of the world’s food crops are affected by mycotoxins, resulting in a widespread human exposure to one or more mycotoxins. They have been suggested to contribute to a diversity of adverse health effects in humans, even at low concentrations. The recognition of multiple mycotoxins being carcinogenic was echoed in recent research and reviews. Therefore, this doctoral dissertation aims to investigate potential associations and to explore causal links between multiple mycotoxins and cancer risk with epidemiological, genomics, transcriptomics and metabolomics approaches. Food questionnaire data from the largest European EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority to assess long-term dietary mycotoxin exposures, whereby possible associations with renal cell, hepatocellular and colorectal carcinoma cancer risk were investigated. The epidemiological evidence suggested associative contributions of the mycotoxins deoxynivalenol (DON) and patulin (PAT) to carcinogenesis in the human liver and colorectum. The possible mechanisms underlying the causative cancer-related effects of DON and PAT were lacking. Therefore, by using comprehensive whole-genome sequencing, we explored the global accumulation of DNA mutations upon chronic treatment of DON and PAT in the clones derived from primary mouse embryonic fibroblasts, liver and colon cell lines. Besides, by using temporal RNA-seq analyses, we investigated the early-response transcriptome remodelling upon exposure to these mycotoxins. Lastly, an UPLC-MS/MS methodology was developed and validated to determine and quantify multiple mycotoxins in human plasma. The obtained results will help to raise awareness of these high-risk contaminants among the general public as well as product development industries and regulatory bodies.

Praktisch

Datum
Vrijdag 23 september 2022, 18:00
Locatie
Faculteit Farmaceutische Wetenschappen - Auditorium A - Claudius Galenus, Ottergemsesteenweg 460, 9000 Gent