8-hydroxy-2--deoxyguanosine and Gastritis--Atrophic

The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Antioxidants; Deoxyguanosine; Dietary Supplements; DNA; DNA Adducts; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Gene Expression Regulation; Humans; Models, Biological; Mucous Membrane; Oxidants; Oxidative Stress; Pilot Projects; Precancerous Conditions; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Up-Regulation; Vitamin E; Vitamins; Xanthine Oxidase

Increased production of reactive oxygen species, which cause oxidative DNA damage, is considered to be related to gastric carcinogenesis. The aim of this research was to detect the 8-OHdG and the expression of hOGG1and MnSOD, in human gastric mucosa with chronic atrophic gastritis (CAG) and gastric carcinoma (GC) comparing with normal controls (NC).. The level of 8-OHdG in gastric biopsy specimens was assessed with immunohistochemistry. The expression level of hOGG1and MnSOD in gastric tissues was assessed with Western blot.. The 8-OHdG staining in CAG and GC mucosa was stronger than control (p<0.01). hOGG1 was expressed to a lower degree in GC and CAG when compared to the control group (both p<0.01) and the level of GC was even lower than CAG (p<0.05). MnSOD was expressed to a greater degree in GC group when compared to the control (p<0.05).. CAG patients who express 8-OHdG highly should be monitored for the potentially occurrence of GC. The lower lever of hOGG1 in CAG and GC with higher level of 8-OHdG implies that hOGG1 is closely related to oxidative DNA damage and may lead to carcinoma. The increasing expression of MnSOD in the gastric mucosa may indicate the occurrence of gastric cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; Biopsy; Blotting, Western; Case-Control Studies; China; Chronic Disease; Deoxyguanosine; DNA Damage; DNA Glycosylases; DNA Repair; Female; Gastric Mucosa; Gastritis, Atrophic; Humans; Immunohistochemistry; Male; Middle Aged; Oxidative Stress; Stomach Neoplasms; Superoxide Dismutase

Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antigens, Bacterial; Atrophy; Bacterial Proteins; Biomarkers, Tumor; Deoxyguanosine; DNA Damage; DNA Glycosylases; Electrophoresis, Gel, Two-Dimensional; Female; Gastritis, Atrophic; Helicobacter pylori; Humans; Intestines; Male; Metaplasia; Middle Aged; Nucleic Acid Amplification Techniques; Oxidative Stress; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prospective Studies; Stomach Neoplasms; Urease