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紫外线辐射诱导皮肤癌变中的表观遗传改变:生物活性膳食成分对表观遗传靶点的相互作用。

Epigenetic alterations in ultraviolet radiation-induced skin carcinogenesis: interaction of bioactive dietary components on epigenetic targets.

机构信息

Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.

出版信息

Photochem Photobiol. 2012 Sep-Oct;88(5):1066-74. doi: 10.1111/j.1751-1097.2011.01020.x. Epub 2011 Nov 17.

Abstract

The importance of epigenetic alterations in the development of various diseases including the cancers has been realized. As epigenetic changes are reversible heritable changes, these can be utilized as an effective strategy for the prevention of cancers. DNA methylation is the most characterized epigenetic mechanism that can be inherited without changing the DNA sequence. Although limited available data suggest that silencing of tumor suppressor genes in ultraviolet (UV) radiation-exposed epidermis leads to photocarcinogenesis and is associated with a network of epigenetic modifications including alterations in DNA methylation, DNA methyltransferases and histone acetylations. Various bioactive dietary components have been shown to protect skin from UV radiation-induced skin tumors in animal models. The role of bioactive dietary components, such as, (-)-epicatechins from green tea and proanthocyanidins from grape seeds has been assessed in chemoprevention of UV-induced skin carcinogenesis and underlying epigenetic mechanism in vitro and in vivo animal models. These bioactive components have the ability to block UV-induced DNA hypermethylation and histone modifications in the skin required for the silencing of tumor suppressor genes (e.g. Cip1/p21, p16(INK4a) ). This information is of importance for understanding the role of epigenetic modulation in UV-induced skin tumor and the chemopreventive mechanism of bioactive dietary components.

摘要

人们已经认识到,表观遗传改变在各种疾病(包括癌症)的发生发展中的重要性。由于表观遗传变化是可逆的可遗传变化,因此可以将其用作预防癌症的有效策略。DNA 甲基化是最具特征性的表观遗传机制,它可以在不改变 DNA 序列的情况下遗传。尽管有限的可用数据表明,紫外线 (UV) 辐射暴露的表皮中肿瘤抑制基因的沉默会导致光致癌,并与包括 DNA 甲基化、DNA 甲基转移酶和组蛋白乙酰化在内的一系列表观遗传修饰网络相关联,但。各种生物活性膳食成分已被证明可在动物模型中保护皮肤免受 UV 辐射诱导的皮肤肿瘤。生物活性膳食成分(例如绿茶中的(-)-表儿茶素和葡萄籽中的原花青素)在化学预防 UV 诱导的皮肤癌发生及其在体外和体内动物模型中的潜在表观遗传机制中的作用已得到评估。这些生物活性成分具有阻断 UV 诱导的皮肤中 DNA 过度甲基化和组蛋白修饰的能力,这是沉默肿瘤抑制基因(例如 Cip1/p21、p16(INK4a))所必需的。这些信息对于了解表观遗传调控在 UV 诱导的皮肤肿瘤中的作用以及生物活性膳食成分的化学预防机制非常重要。

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本文引用的文献

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