Dionne Arthur (PhD Student)
University of Queensland
approach for the assessment of biological effects induced by
completed her Bachelor of Science at the Victoria University of
Wellington, New Zealand majoring in biochemistry and molecular
biology. She completed her Honours at the same university in cell
and molecular bioscience. Dionne is currently enrolled as a PhD
student at the University of Queensland in which her project is
part of a larger one funded by CRC CARE.
reflect changes in biological systems that are related to exposure,
or effects of toxins. The most intuitive need for a biomarker is to
help diagnose disease. The ideal biomarker would be one that
detects stress at an early stage before damage/disease occurs.
Bilirubin oxidative metabolites (BOMs) have been reported to be
elevated in urine and plasma of rats and humans under stress.
Exposure to environmental contaminants has been implicated in the
development of stress. This project aims to establish a
relationship between the concentrations of BOMs found in urine and
plasma with the exposure of environmental contaminants. This will
be performed in a mouse model with the idea that these BOMs can be
used as biomarkers to assess the early response to stress in
mammals. Monitoring toxicity of these contaminants will provide a
realistic approach towards risk assessment with regards to the
health of animals, both aquatic and land-dwelling. The project
outcomes will also provide information that will establish a
platform for the development of a commercial diagnostic kit to
detect urinary and plasma BOMs.
PhD Thesis Abstract - Summary
exposure causes chronic disease and cancer in various organs in
humans. The liver is a target organ for arsenic toxicity. The most
accepted mechanism of arsenic toxicity involves oxidative stress.
The initial response to oxidative stress is defensive, and involves
numerous antioxidant defence systems. Two enzyme systems that have
been reported to play an important role in cellular defence during
metal-induced oxidative stress include haem oxygenase-1 (HO-1) and
cytochrome P450 2a5 (Cyp2a5). It was found that both enzymes are
involved in bilirubin (BR) homeostasis, where Cyp2a5-dependant BR
oxidation is elevated when BR levels increase due to HO-1
induction. The oxidative metabolism of BR is an important pathway
of detoxification in addition to glucuronidation, however the
oxidative products were not identified.
The observations made during the PhD study suggest that (i) both
murine Cyp2a5 and human CYP2A6 enzymes oxidise BR to form BOMs;
(ii) concurrent induction of HO-1 and Cyp2a5 during
arsenic-mediated oxidative stress may protect the liver against
lipid peroxidation; and (iii) production of BOMs may be mediated by
Cyp2a5 BR oxidation and subsequently eliminated in the