8-hydroxy-2--deoxyguanosine and 4-hydroxy-2-hexenal

Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldehydes; Antioxidants; Apoptosis; Blotting, Western; Cell Proliferation; Colorectal Neoplasms; Deoxyguanosine; Disease Progression; Female; Glutathione; Glutathione Peroxidase; Humans; Immunohistochemistry; Male; Malondialdehyde; Oxidative Stress; Proliferating Cell Nuclear Antigen; Selenoprotein P; Selenoproteins; Superoxide Dismutase; Superoxide Dismutase-1; Thioredoxin-Disulfide Reductase; Tumor Suppressor Protein p53

Oxidative stress plays a role in pathogenesis of chronic viral hepatitis. Expression of oxidative stress-related molecules remains to be clarified.. 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase, superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in leukocytes and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in 164 persons, including 130 chronic viral hepatitis patients and 34 normal individuals, by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Hepatic expression of these proteins was immunohistochemically examined in 12 patients with chronic viral hepatitis, compared with three persons without liver damage.. The 4-HNE/beta-actin ratios in chronic viral hepatitis were significantly higher than those in normal individuals (P<0.01), and were significantly correlated with asparate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01, each). The catalase/beta-actin and SOD-1/beta-actin ratios in chronic viral hepatitis were higher than those in normal individuals, and were significantly correlated with 4-HNE/beta-actin ratios (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in chronic viral hepatitis was higher than that without liver damage. Urinary excretion of 8-OHdG was not changed in chronic viral hepatitis.. The results of the present study suggest that expression of oxidative stress-related molecules in leukocytes is upregulated in relation to serum aminotransferase levels.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Alanine Transaminase; Aldehydes; Aspartate Aminotransferases; Blotting, Western; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Hepatitis, Viral, Human; Humans; Leukocytes; Lipid Peroxidation; Liver; Male; Middle Aged; Oxidative Stress; Thioredoxins; Up-Regulation