Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels.
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.
Dyke
G W
GW
Jack Birch Unit for Environmental Carcinogenesis, Department of Biology, University of York, UK.
Craven
J L
JL
Hall
R
R
Garner
R C
RC
D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002908:Chronic Disease; D004260:DNA Repair; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D005757:Gastritis, Atrophic / Q000201:enzymology*; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013270:Stomach / Q000187:drug effects / Q000201:enzymology*
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D001205:Ascorbic Acid