GENETOXIC RESPONSE TO OXIDATIVE DAMAGE

氧化应激，由细胞暴露在“活性氧”中引起 物种(AO)，是急性和慢性细胞损伤的主要原因。 AO的细胞内靶点包括蛋白质、脂类和DNA。损坏 这些细胞成分代表着对有机体的系统性挑战。 也许甚至是潜伏在它自己身上的。在细菌中，许多基因涉及三个 不同的调节子，oxR，soxR和recA，已经被证明在 对氧化应激的反应。人们对此知之甚少 高等生物体对氧化损伤的遗传反应。在这个项目中 我们已经开始研究对氧化剂的急性遗传反应。 全肺及培养的肺成纤维细胞和内皮细胞的损伤 暴露在高氧条件下的细胞。到目前为止，我们已经展示了几个 在细胞暴露24小时内在肺成纤维细胞中诱导基因 至95%的高氧血症。其中包括已知的抗氧化剂过氧化氢酶和 超氧化物歧化酶，诱导3-5倍，和另外两个基因， Gadd153和血红素加氧酶，它们被诱导为基础水平的20-40倍 级别。这些基因的蛋白质产物很可能是 对氧化损伤的保护性或修复性反应。

Oxidative stress, resulting from the exposure of cells to "active oxygen" species (AO), is a major cause of both acute and chronic cell injury. Intracellular targets of AO include proteins, lipids, and DNA. Damage to these cellular constituents represents a systemic challenge to the organism perhaps even underlying itself. In bacteria, many genes involving three distinct regulons, oxyR, soxR, and recA, have been shown to be induced in response to oxidative stress. Comparatively little is known about the genetic response to oxidative damage in higher organisms. In this project we have initiated studies to examine the acute genetic response to oxidant damage in the whole lung and in cultured lung fibroblast and endothelial cells exposed to hyperoxic conditions. So far we have shown that several genes are induced in lung fibroblasts within 24 hours of exposure of cells to 95% hyperoxia. These include the known antioxidants catalase and superoxide dismutase, which are induced 3-5 fold, and two additional genes, gadd153 and heme oxygenase, which are induced 20-40 fold above the basal levels. It is likely that the protein products of these genes are part of the protective or repartive response to oxidant injury.