title: Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with lipid peroxidation, ascorbic acid, and Helicobacter pylori.
abstract: Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.
authors.affiliation: Centre for Digestive Diseases, The General Infirmary and Academic Unit of Epidemiology and Health Services Research, Leeds LS9 7TF, United Kingdom.
authors.forename: S M
authors.initials: SM
authors.lastname: Everett
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Leuratti
authors.forename: K L
authors.initials: KL
authors.lastname: White
authors.forename: P
authors.initials: P
authors.lastname: Neville
authors.forename: D
authors.initials: D
authors.lastname: Greenwood
authors.forename: L J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: C J
authors.initials: CJ
authors.lastname: Schorah
authors.forename: D
authors.initials: D
authors.lastname: Forman
authors.forename: D
authors.initials: D
authors.lastname: Shuker
authors.forename: A T
authors.initials: AT
authors.lastname: Axon
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis*; D004724:Endoscopy; D005260:Female; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000737:chemistry* / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007118:Immunoassay; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged
chemical_list: C089188:3-(2'-deoxyribofuranosyl)pyrimido(1,2-a)purin-10(3H)-one; D003849:Deoxyguanosine; D001205:Ascorbic Acid