Gw. Dyke et al., EFFECT OF VITAMIN-C UPON GASTRIC-MUCOSAL O-6-ALKYLTRANSFERASE ACTIVITY AND ON GASTRIC VITAMIN-C LEVELS, Cancer letters, 86(2), 1994, pp. 159-165
The repair enzyme O-6-alkyltransferase will repair O-6-methylguanine a
dducts in human DNA. In gastric mucosal DNA these adducts may be forme
d as a result of exposure to nitrosamines within the gastric lumen. Th
e formation of these nitrosamines may be inhibited by vitamin C. We ha
ve examined the effect of oral vitamin C supplementation upon intragas
tric vitamin C levels and gastric mucosal O-6-alkyltransferase levels
in 48 patients. Intragastric vitamin C levels were significantly eleva
ted in those patients with normal gastric mucosal histology after trea
tment, although a variable response in intragastric vitamin C to suppl
ementation was seen in the presence of chronic atrophic gastritis. Gas
tric mucosal O-6-alkyltransferase activities ranged from 100 to 950 fm
ol/mg protein before vitamin C administration. The range of enzyme act
ivity was similar after the course of vitamin C (62-1137 fmol/mg) but
O-6-alkyltransferase activities were found to be higher in 33 of the 4
8 patients following treatment (P < 0.01). Once again this effect was
more pronounced in patients with normal gastric mucosa than those disp
laying evidence of chronic atrophic gastritis. We speculate that inhib
ition of intragastric nitrosation by vitamin C results in decreased fo
rmation of O-6-methylguanine-DNA. In consequence, less O6-alkyltransfe
rase is consumed in repairing these adducts resulting in higher tissue
levels of this enzyme.