DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation.
DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation.
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DOI：
10.1097/00008469-199411000-00004
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发表时间：
1994-11-01
期刊：
影响因子：
--
通讯作者：
Leitao, C N
中科院分区：
文献类型：
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作者：
Cravo, M;Fidalgo, P;Leitao, C N
多项研究表明 DNA 低甲基化是结直肠癌发生的早期步骤。然而，目前尚不清楚这种低甲基化发生在癌发生的哪个阶段，是什么促进了它，它可以逆转的程度以及这种逆转对肿瘤发展的影响。为了解决其中一些问题，我们研究了三组具有相似年龄和性别分布的受试者：一组为 12 名结直肠癌患者；一组12名结直肠腺瘤患者；以及一组八名健康对照受试者。采用了两种实验方案。在第一个方案中，与一组健康对照相比，对结肠癌或腺瘤患者的肿瘤和外观正常的直肠粘膜的内在 DNA 甲基化进行了评估。在第二个方案中，我们以前瞻性和对照的方式检查了叶酸补充剂（10 毫克/天）对肿瘤切除后同一患者直肠粘膜 DNA 甲基化程度的影响。根据DNA分离物在含有DNA甲基化酶和[3H-甲基]S-腺苷甲硫氨酸的体外培养中充当甲基受体的能力来评估内在DNA甲基化的程度。癌中的内在 DNA 甲基化显着低于腺瘤 (P < 0.005)。此外，癌症患者的直肠粘膜外观正常，其甲基化程度显着低于健康对照（P < 0.005）；后者的平均值也大于腺瘤患者中观察到的值，但差异不显着（P > 0.05）。（摘要截断为 250 字）
Several studies have suggested that DNA hypomethylation is an early step in colorectal carcinogenesis. However, it is not clear at which stage in carcinogenesis this hypomethylation occurs, what promotes it, the extent to which it can be reversed and the consequences of such reversal in affecting tumour development. In an attempt to address some of these questions, we studied three groups of subjects with similar age and gender distributions: a group of 12 patients with colorectal carcinomas; a group of 12 patients with colorectal adenomas; and a group of eight healthy control subjects. Two experimental protocols were employed. In the first protocol, intrinsic DNA methylation was evaluated in neoplastic and in normal-appearing rectal mucosa of patients with colonic carcinomas or adenomas, compared with a group of healthy controls. In the second protocol, we examined, in a prospective and controlled fashion, the effect of folic acid supplementation (10 mg/day) on the degree of DNA methylation of rectal mucosa from those same patients after removal of the neoplasms. The degree of intrinsic DNA methylation was assessed on the basis of the capacity of the DNA isolates to serve as methyl acceptors in in vitro incubations that contained DNA methylase and [3H-methyl] S-adenosylmethionine. Intrinsic DNA methylation was significantly lower in carcinomas than in adenomas (P < 0.005). In addition, normal-appearing rectal mucosa from patients with carcinomas was significantly less methylated than in healthy controls (P < 0.005); the mean value found in the latter was also greater than the value observed in patients with adenomas, but not significantly so (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)