Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene
Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene
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DOI：
10.1093/ajcn/65.1.46
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发表时间：
1997-01-01
影响因子：
7.1
通讯作者：
Mason, JB
中科院分区：
文献类型：
--
作者：
Kim, YI;Pogribny, IP;Mason, JB
叶酸对于嘌呤和胸苷酸的从头生物合成是必需的，并且是DNA甲基化的甲基转移的重要介质。因此，叶酸缺乏可能导致异常的DNA完整性和甲基化模式。我们研究了大鼠叶酸缺乏对DNA甲基化和DNA链断裂的影响，无论是在基因组水平上还是在p53肿瘤抑制基因的特定序列内。我们的数据表明，叶酸缺乏诱导DNA链断裂和p53基因内的低甲基化。当在全基因组的基础上进行检查时，这种改变要么没有发生，要么在时间上延迟，表明p53基因内检查的外显子具有一定的选择性。叶酸不足与几种人类和实验性癌症的发展有关，本研究中检查的p53基因这些区域内的畸变被认为在致癌作用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手段。
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.