美国强制添加叶酸与子宫颈中DNA甲基转移酶-1表达增加有关。
Mandatory fortification with folic acid in the United States is associated with increased expression of DNA methyltransferase-1 in the cervix.
作者信息
Piyathilake Chandrika J, Celedonio Jorge E, Macaluso Maurizio, Bell Walter C, Azrad Maria, Grizzle William E
机构信息
Department of Nutrition Sciences, The University of Alabama at Birmingham, Alabama, USA.
出版信息
Nutrition. 2008 Jan;24(1):94-9. doi: 10.1016/j.nut.2007.10.007.
OBJECTIVE
The objective of this study was to evaluate whether mandatory fortification of grain products with folic acid in the United States is associated with changes in DNA methyltransferase-1 (Dnmt-1) expression in cells involved in cervical carcinogenesis.
METHODS
Archived specimens of cervical intraepithelial neoplasia (CIN) diagnosed before (1990-1992) and after (2000-2002) mandatory folic acid fortification were used to examine the expression of Dnmt-1 in specific lesions involved in cervical carcinogenesis by immunohistochemistry. The total number of lesions examined was 101 in the prefortification period and 96 in the postfortification period. Immunohistochemical staining for Dnmt-1, its assessment, and data entry were blinded with regard to the fortification status.
RESULTS
Age- and race-adjusted mean percentage of cells positive for Dnmt-1 or the Dnmt-1 score was significantly higher in all lesion types (i.e., normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN, or carcinoma in situ) detected in the postfortification period compared with the prefortification period (P < 0.05, all comparisons). The degree of Dnmt-1 was significantly higher (P < 0.0001) in CIN > or = 2 lesions compared with CIN < or = 1 lesions, regardless of the fortification group.
CONCLUSION
These results suggest that mandatory fortification with folic acid in the United States seems to have resulted in a change in the degree of expression of Dnmt-1 in cells involved in cervical carcinogenesis. Because the approach we have taken to demonstrate these differences have limitations inherent to a study of this nature and this is the first study to report a folate fortification associated change in Dnmt-1, validating these results in other study populations and/or with other techniques of assessing Dnmt-1 will increase the scientific credibility of these findings.
目的
本研究的目的是评估美国强制在谷物产品中添加叶酸是否与宫颈癌发生相关细胞中DNA甲基转移酶-1（Dnmt-1）表达的变化有关。
方法
使用在强制添加叶酸之前（1990 - 1992年）和之后（2000 - 2002年）诊断的宫颈上皮内瘤变（CIN）存档标本，通过免疫组织化学检查Dnmt-1在宫颈癌发生相关特定病变中的表达。强化前检查的病变总数为101个，强化后为96个。Dnmt-1的免疫组织化学染色、评估和数据录入对强化状态进行了盲法处理。
结果
与强化前相比，强化后检测到的所有病变类型（即正常宫颈上皮、反应性宫颈上皮、化生宫颈上皮、CIN或原位癌）中，Dnmt-1阳性细胞的年龄和种族调整后平均百分比或Dnmt-1评分显著更高（所有比较，P < 0.05）。无论强化组如何，与CIN≤1级病变相比，CIN≥2级病变中Dnmt-1的程度显著更高（P < 0.0001）。
结论
这些结果表明，美国强制添加叶酸似乎导致了宫颈癌发生相关细胞中Dnmt-1表达程度的变化。由于我们用来证明这些差异的方法具有这类研究固有的局限性，且这是第一项报告叶酸强化与Dnmt-1变化相关的研究，在其他研究人群中使用其他评估Dnmt-1的技术验证这些结果将提高这些发现的科学可信度。
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