title: Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals.
abstract: High dietary ascorbic acid intake appears to protect against gastric cancer. This may be due to its action as a scavenger of reactive radical species formed in the gastric mucosa, resulting in a reduced level of radical-mediated DNA damage. We have studied 82 patients, of whom 37 had Helicobacter pylori-associated gastritis, a condition which predisposes to gastric cancer. Using electron paramagnetic resonance (EPR) spectroscopy we have demonstrated, for the first time, that ascorbyl radicals are generated in human gastric mucosa, presumably as a result of scavenging of free radicals by ascorbic acid. Quantification of ascorbyl radicals demonstrates that there is a higher concentration in those patients with H.pylori gastritis compared with subjects with normal histology (P < 0.01). We also found gastric mucosal luminol-enhanced chemiluminescence and malondialdehyde concentrations (which are believed to be markers of radical generation and tissue damage) to be higher in patients with H.pylori gastritis compared with those with normal histology (P < 0.001 and P < 0.01 respectively). The observed concentrations of the ascorbyl radical correlate with the level of luminol-enhanced chemiluminescence (r = 0.41, P < 0.001), but not with malondialdehyde concentrations (r = 0.08, P = 0.47). Mucosal ascorbic acid and total vitamin C concentrations did not vary between histological groups, nor did they correlate with mucosal levels of the ascorbyl radical, chemiluminescence or malondialdehyde. These data suggest that ascorbic acid is acting as a scavenger of free radicals generated in human gastric mucosa. The experiments therefore provide direct supportive evidence for the hypothesis that ascorbic acid protects against gastric cancer by scavenging reactive radical species which would otherwise react with DNA, with resultant genetic damage.
authors.affiliation: The Centre for Digestive Diseases, The General Infirmary at Leeds, UK.
authors.forename: I M
authors.initials: IM
authors.lastname: Drake
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.forename: N P
authors.initials: NP
authors.lastname: Mapstone
authors.forename: M F
authors.initials: MF
authors.lastname: Dixon
authors.forename: C J
authors.initials: CJ
authors.lastname: Schorah
authors.forename: K L
authors.initials: KL
authors.lastname: White
authors.forename: D M
authors.initials: DM
authors.lastname: Chalmers
authors.forename: A T
authors.initials: AT
authors.lastname: Axon
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism*; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism*; D005756:Gastritis / Q000382:microbiology; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008163:Luminescent Measurements; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D001205:Ascorbic Acid