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.