为进一步明确人胃癌发生中维生素含量和DNA甲基化水平与模式的变化及维生素对癌前疾病的干预作用,我们①以微量生化法检测了56例慢性萎缩性胃炎(CAG)、6例胃溃疡和27例胃癌及45例健康成人的血浆维生素A、C、E、β-胡萝卜素和叶酸、 维生素B12 及部分检测了供应病灶的动脉和所属静脉血中维生素及胃手术标本不同部位和活检胃粘膜细胞内β-胡萝卜素、组织内叶酸的变化。 ②分别采用甲基化酶孵育、 3H-SAM掺入法及Southernblot法观察了CAG、胃癌患者总基因组DNA、c-myc、c-Ha-ras癌基因的DNA甲基化水平的改变等。③分别以天然β-胡萝卜素、合成β-胡萝卜素及叶酸对中重度CAG行临床干预。结果表明, 胃癌患者血浆、胃粘膜细胞的维生素A、C、E、β-胡萝卜素显低于正常人; 其总基因组DNA甲基化水平下降, 癌区和癌旁区的c-myc、c-Ha-ras 癌基因片段DNA甲基化水平下降, 且甲基化水平降低情况与血浆叶酸降低有关。CAG经β-胡萝卜素和叶酸干预半年后, 血及胃粘膜组织和细胞内相应的维生素升高及总基因组DNA甲基化水平上升, 异型增生、肠上皮化生改善明显。

Name: Jing-Yuan Fang. Date of birth:December 1961. Tutor: Prof.Shao-Ji Jiang, Prof.Shu-Dong Xiao. Date of graduation:July 1996. Subject: Medicine, Gastroenterology.

In order to further explore the effect of vitamins in carcinogenesis of gastric cancer(GC), The concentrations of vitamins A,C, E, β-carotene, folic acid and vitamin B12 were measured in patients with CAG and GC. And examined the levels of total genomic DNA and c-myc,c-Ha-ras oncogene methylation, 56 patients with CAG were enrolled randomly into 4 groups treated with natural β-carotene,synthetic β-carotene,folic acid and placebo, respectively.The results show that in patients with GC plasma, tissue concentration of vitamins A,C,E,β-carotene were significantly lower than those in healthy subjects. The levels total gnomic DNA c-myc, c-Ha-ras oncogenes methylation were reduced in cancerous, paracanerous areas. All these changes were related with the reduction of plasma folic acid. After treatment, the total genomic DNA methylation was enhanced, and the histopathology improved remarkably in patients with CAG.