Dyke G W, Craven J L, Hall R, Garner R C
Jack Birch Unit for Environmental Carcinogenesis, Department of Biology, University of York, UK.
Cancer Lett. 1994 Nov 11;86(2):159-65. doi: 10.1016/0304-3835(94)90074-4.
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.
修复酶O6-烷基转移酶可修复人类DNA中的O6-甲基鸟嘌呤加合物。在胃黏膜DNA中，这些加合物可能是由于胃腔内接触亚硝胺而形成的。维生素C可能会抑制这些亚硝胺的形成。我们检测了48例患者口服补充维生素C对胃内维生素C水平和胃黏膜O6-烷基转移酶水平的影响。治疗后，胃黏膜组织学正常的患者胃内维生素C水平显著升高，不过在存在慢性萎缩性胃炎的情况下，胃内维生素C对补充的反应存在差异。在给予维生素C之前，胃黏膜O6-烷基转移酶活性范围为100至950 fmol/mg蛋白质。在维生素C疗程后，酶活性范围相似（62 - 1137 fmol/mg），但在48例患者中有33例在治疗后O6-烷基转移酶活性升高（P < 0.01）。同样，这种效应在胃黏膜正常的患者中比那些有慢性萎缩性胃炎证据的患者更明显。我们推测维生素C对胃内亚硝化作用的抑制导致O6-甲基鸟嘌呤-DNA形成减少。因此，在修复这些加合物时消耗的O6-烷基转移酶减少，导致该酶在组织中的水平升高。
