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Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels.

Abstract
The repair enzyme O6-alkyltransferase will repair O6-methylguanine adducts in human DNA. In gastric mucosal DNA these adducts may be formed as a result of exposure to nitrosamines within the gastric lumen. The formation of these nitrosamines may be inhibited by vitamin C. We have examined the effect of oral vitamin C supplementation upon intragastric vitamin C levels and gastric mucosal O6-alkyltransferase levels in 48 patients. Intragastric vitamin C levels were significantly elevated in those patients with normal gastric mucosal histology after treatment, although a variable response in intragastric vitamin C to supplementation was seen in the presence of chronic atrophic gastritis. Gastric mucosal O6-alkyltransferase activities ranged from 100 to 950 fmol/mg protein before vitamin C administration. The range of enzyme activity was similar after the course of vitamin C (62-1137 fmol/mg) but O6-alkyltransferase activities were found to be higher in 33 of the 48 patients following treatment (P < 0.01). Once again this effect was more pronounced in patients with normal gastric mucosa than those displaying evidence of chronic atrophic gastritis. We speculate that inhibition of intragastric nitrosation by vitamin C results in decreased formation of O6-methylguanine-DNA. In consequence, less O6-alkyltransferase is consumed in repairing these adducts resulting in higher tissue levels of this enzyme.
AuthorsG W Dyke, J L Craven, R Hall, R C Garner
JournalCancer letters (Cancer Lett) Vol. 86 Issue 2 Pg. 159-65 (Nov 11 1994) ISSN: 0304-3835 [Print] Ireland
PMID7982203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Ascorbic Acid
Topics
  • Ascorbic Acid (metabolism, pharmacology)
  • Chronic Disease
  • DNA Repair
  • Gastric Mucosa (drug effects, enzymology)
  • Gastritis, Atrophic (enzymology)
  • Humans
  • Methyltransferases (metabolism)
  • O(6)-Methylguanine-DNA Methyltransferase
  • Stomach (drug effects, enzymology)

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