| dc.description.abstract | The cell's genomic integrity is essential for all life forms, and is constantly being exposed to both
endogenous and exogenous threats. In order to preserve this integrity, through evolution, the cells have
developed a toolbox of biomechanisms which collectively make up the cells’ DNA damage response. One
of these mechanisms is DNA repair; consisting of an extensive network of repair proteins, specialized in
repairing DNA damage. The daily amount of DNA damage induced in each cell can be as much as 105
lesions. Accumulation of DNA damage over time trigger genomic instability, which is a hallmark of cancer.
Reactive oxygen and nitrogen species (RONS) are among the most common sources of DNA damage.
Ulcerative colitis is an intestinal disease caused by chronic idiopathic inflammation, affecting the colon to a
varying extent and degree. Oxidative and nitrative stress in chronic inflamed tissue promotes a tumor
microenvironment that accelerates the increased production of RONS. As a result, the concentration of
DNA damage is high in the colon epithelia of UC patients. It is believed that high concentrations of DNA
damage are an important predisposing factor for the progression to colitis-associated colorectal cancer
(CAC) in UC-patients. Unlike sporadic colorectal cancer (CRC), CAC is more frequent in younger
individuals as progression from dysplastic UC to CAC may advance faster compared to the more
prolonged progression of sporadic CRC.
In a previous study, our research group has used immunohistochemistry, digital pathology, and semiquantitative
cell counting to study the expression pattern of the NUCKS1 DNA double-strand break repair
protein in colon biopsies from patients with UC and sporadic CRC. An inverse correlation between
NUCKS1 expression and disease progression was demonstrated. In this study we looked at the
expression pattern of PARP1 in the same groups of patients. PARP1 is an enzyme which catalyzes the
transfer of polymer chains with ADP-ribose units to target proteins involved in DNA repair. This transferase
activity is an important post-transnational modification that initiates DNA repair when PARP1 senses DNA
damage. Although PARP1 is biologically multifunctional, it is best known for its function as DNA nicksensor
in the base-excision repair pathway. Our results from this study show that the PARP1 expression is
generally increased in both UC and CRC. However, when we compared the levels of PARP1 expression
in both diseases, we observed that UC lesions displayed a stronger level of PARP1 expression than CRC
(p<0.05), which could indicate that PARP1 and DNA repair may be critically involved in the UC
pathogenesis. | en |
