“MicroRNAs and epigenetics in chemical carcinogenesis”

Supervisor:

• prof.dr. J.C.S. Kleinjans

Co-supervisor:

• dr. S.G.J. van Breda

This dissertation describes an alternative test method for the detection of carcinogenic substances using cells grown in Petri dishes. In this research project, human and mouse liver cells were exposed to carcinogenic and control substances. An expression pattern of messenger molecules (mRNA molecules) was found which have the capacity to make a distinction between different carcinogenic exposures. By using an innovative approach, different biological levels (epigenome, transcriptome and microRNAome) were integrated which provide more insight into the working mechanism of these carcinogenic substances. These results can be linked to a similar type of expression pattern in patients suffering from liver cancer. In the future, the new findings can result in an improved cancer risk assessment of new chemical substances, therefore reducing the need for animal experiments.

Key words:
liver cancer, alternative test method, expression pattern