Kim Y I, Pogribny I P, Basnakian A G, Miller J W, Selhub J, James S J, Mason J B
Vitamin Bioavailability Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, USA.
Am J Clin Nutr. 1997 Jan;65(1):46-52. doi: 10.1093/ajcn/65.1.46.
Folate is essential for the de novo biosynthesis of purines and thymidylate, and is an important mediator in the transfer of methyl groups for DNA methylation. Folate deficiency, therefore, could contribute to abnormal DNA integrity and methylation patterns. We investigated the effect of isolated folate deficiency in rats on DNA methylation and DNA strand breaks both at the genomic level and within specific sequences of the p53 tumor suppressor gene. Our data indicate that folate deficiency induces DNA strand breaks and hypomethylation within the p53 gene. Such alterations either did not occur or were chronologically delayed when examined on a genome-wide basis, indicating some selectivity for the exons examined within the p53 gene. Folate insufficiency has been implicated in the development of several human and experimental cancers, and aberrations within these regions of the p53 gene that were examined in this study are thought to play an integral role in carcinogenesis. The aforementioned molecular alterations may therefore be a means by which dietary folate deficiency enhances carcinogenesis.
叶酸对于嘌呤和胸苷酸的从头生物合成至关重要，并且是DNA甲基化过程中甲基转移的重要介质。因此，叶酸缺乏可能导致DNA完整性和甲基化模式异常。我们研究了大鼠单纯叶酸缺乏对基因组水平以及p53肿瘤抑制基因特定序列内DNA甲基化和DNA链断裂的影响。我们的数据表明，叶酸缺乏会诱导p53基因内的DNA链断裂和低甲基化。当在全基因组范围内进行检测时，此类改变要么未发生，要么在时间上延迟出现，这表明对p53基因内所检测的外显子具有一定的选择性。叶酸不足与多种人类和实验性癌症的发生有关，本研究中所检测的p53基因这些区域内的畸变被认为在致癌过程中起着不可或缺的作用。因此，上述分子改变可能是膳食叶酸缺乏增强致癌作用的一种方式。
