DOCTORAL CANDIDATE:
Mazyar Yazdani
DEGREE:
Philosophiae Doctor
FACULTY:
Faculty of Mathematics and Natural Sciences
DEPARTMENT:
Department of Biosciences
AREA OF EXPERTISE:
Toxicology
SUPERVISORS:
Ketil Hylland, Ragnhild Elisabeth Paulsen and Tor
Gjøen
7th of February 2014
DATE OF DISPUTATION:
DISSERTATION TITLE:
In vitro, in ovo and in vivo models for cytotoxicity,
oxidative stress, neurotoxicity and DNA damage
The adverse biological effects of environmental contaminants are conventionally investigated
using whole-animal experiments, known as in vivo. Since the mid 1980s, ethical and
economical issues have encouraged the development of alternative methods using cell culture
techniques, called in vitro. This resulted in increased use of methods not requiring intact
organisms. However, they have limitations and need to be improved. Despite increasing
interest in the application of cell cultures, in vivo methods still provide valuable information,
particularly for neurodevelopmental toxicity. In addition to this, another experimental
approach in examining potential adverse effect on early live stage is using egg, called in ovo.
First part of this thesis demonstrated the successful establishment of cell cultures from liver of
three marine fish species plaice, long rough dab and Atlantic cod using a two-step liver
perfusion technique. Cultured hepatocytes from flatfish were found to be more susceptible to
the test compounds (statins and copper) than cod hepatocytes. In order to investigate the
influence of exposure conditions on cellular damages and cellular defense mechanisms, the
hepatocyte cultures from rainbow trout were used. Both choice of medium and culture age
affected the cellular responses to oxidative damage caused by model compound (copper).
Trout hepatocytes were furthermore used to investigate mechanisms of DNA damage after
exposure to selected polycyclic aromatic hydrocarbons (PAHs), ubiquitous aquatic
contaminants. Levels of damage to DNA were not clearly linked to oxidative stress. In
addition, the results revealed CYP1A, active enzyme in metabolism of PAHs, independent
mechanisms of genotoxicity.
In the last part of the thesis, neurodevelopmental toxicity of bisphenol-A, largely produced
and consumed compound in plastic products, was studied using two model systems: mice and
chicken embryo. Prenatal exposure to BPA perturbed cerebellar morphology and altered the
level of desired marker of toxicity, Pax6.