Oxidative stress in ulcerative colitis-associated carcinogenesis
Section snippets
Basic principles of oxidative life
When life developed, the atmosphere of the planet was considerably different from the present atmosphere, as there was no oxygen in it. Therefore, the early organisms in evolution were anaerobic. In the course of evolution, cyanobacteria developed which are capable of photosynthesis. With the energy adopted by photosynthesis, they split water and reduce CO2 to carbohydrates. As a by-product of this reaction, they synthesize O2, which has accumulated in the atmosphere to the current atmospheric
Impact of ROS on DNA
Oxidation of DNA by ROS can result in damage to all four bases and to the deoxy-ribose-molecule. The DNA base products of interaction with ROS are manifold and comprise a great variety of modified DNA molecules, which need not be discussed at the chemical level in detail here in this context [5], [24]. One of the most abundant molecules which is a product of this oxidation is 8-oxo-7,8-dihydro-2,-deoxyguanosine (8-OH-dG). This molecule is of practical importance because it can easily be
Antioxidant defense mechanisms
Among the antioxidant defenses in the human body enzymes play a major role [52]. Superoxide dismutases (SOD) are the particularly important ones, i.e., the mitochondrial MnSOD and the largely cytosolic CuZnSOD. The SODs form a mutually supportive group of enzymes with peroxydases and catalases to provide a defense against different ROS [45], [57], [83], [85]. SODs can convert O2-radicals into O2 and H2O2. H2O2 is then further metabolized by the peroxidases and catalases. Of these, glutathione
Role of ROS in cell signaling
It has been known for a long time that bacteria respond to changes in the concentration of ROS in their environment with a precise signaling pathway and a corresponding pattern of gene expression [7]. The last few years have shown that ROS do not have only toxic effects in mammalian cells but also have an important role as signaling molecules, which regulate many genes. Among the ligands of ROS are inflammatory cytokines, growth factors coupled to receptor tyrosine kinases, and ligands
Sources of ROS in preneoplasias and tumors
It has been estimated that nearly 20% of the global human cancers are attributable to infective and inflammatory diseases [109]. The most important cancers with infection etiology are gastric cancer and Helicobacter pylori gastritis, hepatocellular carcinoma and chronic HBV or HCV infection of the liver or parasitic infection of the liver such as liver flukes, as well as parasitic infection by schistosoma haematobium and bladder cancer [65].
Inflammatory diseases with non-infective etiology have
Occurrence and etiology of inflammatory bowel disease
Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of IBD. They are characterized by a recurrent chronic inflammation in the bowel wall. Both UC and CD can pave the way for colorectal cancer. In the United States, about 30,000 new cases of IBD are reported each year [55]. The risk of developing colorectal cancer in UC is estimated as 2.5% after 20 years, 7.6% after 30 years, and 10.8% after 40 years [119]. In CD, the estimation of cancer risk has been controversial over
Conclusions
In the last few years, the molecular mechanisms of IBD-related carcinogenesis could well be established. Their hallmarks are as follows: inflammatory infiltration leading to increased production of ROS, impairment of antioxidant defenses resulting in oxidative stress following lipid peroxidation, DNA damage, and genetic and epigenetic alterations in the transforming epithelial cells, eventually resulting in colorectal cancer. The description of these molecular mechanisms has profoundly improved
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