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首页> 外文期刊>Cell and Tissue Research >Cell-type-specific level of DNA nucleotide excision repair in primary human mammary and ovarian epithelial cell cultures.
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Cell-type-specific level of DNA nucleotide excision repair in primary human mammary and ovarian epithelial cell cultures.

机译：DNA核苷酸切除修复的细胞类型特异性水平在原代人的乳腺和卵巢上皮细胞培养物中。

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DNA repair, a fundamental function of cellular metabolism, has long been presumed to be constitutive and equivalent in all cells. However, we have previously shown that normal levels of nucleotide excision repair (NER) can vary by 20-fold in a tissue-specific pattern. We have now successfully established primary cultures of normal ovarian tissue from seven women by using a novel culture system originally developed for breast epithelial cells. Epithelial cells in these cultures aggregated to form three-dimensional structures called "attached ovarian epispheres". The availability of these actively proliferating cell cultures allowed us to measure NER functionally and quantitatively by the unscheduled DNA synthesis (UDS) assay, a clinical test used to diagnose constitutive deficiencies in NER capacity. We determined that ovarian epithelial cells manifested an intermediate level of NER capacity in humans, viz., only 25% of that of foreskin fibroblasts, but still 2.5-fold higher than that of peripheral blood lymphocytes. This level of DNA repair capacity was indistinguishable from that of normal breast epithelial cells, suggesting that it might be characteristic of the epithelial cell type. Similar levels of NER activity were observed in cultures established from a disease-free known carrier of a BRCA1 truncation mutation, consistent with previous normal results shown in breast epithelium and blood lymphocytes. These results establish that at least three "normal" levels of such DNA repair occur in human tissues, and that NER capacity is epigenetically regulated during cell differentiation and development.
机译：DNA修复是细胞新陈代谢的基本功能，长期以来一直被认为在所有细胞中都是组成性的和等同的。但是，我们以前已经表明，正常的核苷酸切除修复（NER）水平可以以组织特异性模式变化20倍。现在，我们已经使用最初为乳腺上皮细胞开发的新型培养系统，成功地从7名妇女中建立了正常卵巢组织的原代培养。这些培养物中的上皮细胞聚集形成称为“附着的卵巢表层球”的三维结构。这些活跃增殖的细胞培养物的可用性使我们能够通过计划外的DNA合成（UDS）分析在功能上和定量上测量NER，这是一种用于诊断NER能力组成型缺陷的临床测试。我们确定卵巢上皮细胞在人类中表现出中等水平的NER能力，即只有包皮成纤维细胞的25％，但仍比外周血淋巴细胞高2.5倍。这种水平的DNA修复能力与正常的乳腺上皮细胞没有区别，这表明它可能是上皮细胞类型的特征。在从无病的已知BRCA1截短突变载体中建立的培养物中，观察到了类似的NER活性水平，这与以前在乳腺上皮和血液淋巴细胞中显示的正常结果一致。这些结果表明，在人体组织中至少有3种“正常”水平的DNA修复发生，并且NER的能力在细胞分化和发育过程中由表观遗传调控。

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