叶酸阻断胃癌形成机理的初步研究

目的:进一步明确叶酸抗萎缩性胃炎和阻断人胃癌发生发展的分子机理。方法:将25例慢性萎缩性胃炎(CAG)病人随机分组,分别用叶酸和安慰剂治疗半年,以放免法观察血浆和胃粘膜组织内叶酸浓度的变化,分别以H-SAM掺入,液闪计数法和HpaⅡ/Mspl酶解,Southern blot法研究其胃癌区、癌旁和外周正常区的总基因组DNA与c-myc癌基因甲基化水平的改变。结果:叶酸(FA)组萎缩性胃炎患者治疗后血浆FA含量明显上升,萎缩和肠化改善显著,两者呈同步变化;治疗后FA组DNA掺入甲基的量明显减少(P<0.01).即其总基因组DNA甲基化水平上升,与血浆叶酸的升高相一致;胃癌病人手术标本甲基化水平的分析显示:c-myc片段低甲基化者,叶酸水平明显低于正常甲基化者(P<0.05)。结论:叶酸对CAG的组织病理具有显著的改善作用。

Preliminary Study of the Mechanism of Folic Acid on Human Gastric Carcinogenesis

Background/Aims: To further explore the mechanism that folic acid (FA) might regress human gastric carcinogenesis. Methods: The histopathological changes and the alterations of plasma and gastric mucosal tissue FA concentration were observed during the treatment in 25 patients with chronic atrophic gastritis (CAG). These patients were ramdomly divided into 2 groups and were treated with FA and placebo respetively for 6 months. At the same time, the level of global genomic DNA methylation was examined by incubation with 3H-S-adenoslymethionine (3H-SAM) in the presence of methylase, and the methylation status of c-myc oncogene fragment containing CCGG sequence was measured by Southern blot in 22 patients with GC. Results: The plasma and mucosal tissue FA concentrations were significantly higher than that in controls after the treatment, and the FA was most effective for atrophy and intestinal metaplasia (P<0.05); moreover, the level of global genomic DNA methylation was significantly enhanced after the treatment. The plasma FA concentrations in hypomethylated cases were lower than the normal methylated cases in patients with GC. Conclasions: FA affects gastric carcinogenesis, its mechanism is probably related with the DNA methylation status.