Depletion of mitochondrial DNA and enzyme in estrogen-induced hamster kidney tumors: a rodent model of hormonal carcinogenesis.
Depletion of mitochondrial DNA and enzyme in estrogen-induced hamster kidney tumors: a rodent model of hormonal carcinogenesis.
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雌激素诱导的仓鼠肾肿瘤中线粒体 DNA 和酶的消耗：激素致癌的啮齿动物模型。
DOI：
10.1002/jbt.10017
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Bhat,HariK
中科院分区：
文献类型：
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作者：
Bhat,HariK
线粒体 DNA (mtDNA) 编码 13 种对电子传递链正常功能至关重要的多肽，mtDNA 的损伤与衰老有关，并与多种疾病过程有关。尽管线粒体DNA损伤与突变和致癌有关，但证明线粒体DNA损伤在人类或啮齿动物癌症中的作用和程度的研究有限。使用系列稀释和竞争性聚合酶链反应分析，我们定量了总 mtDNA 的量，并分析了雌激素诱导和雌激素依赖性仓鼠肾肿瘤中 mtDNA 损伤的程度。仓鼠肾肿瘤模型是一种有用且广泛研究的激素致癌作用啮齿动物模型，其与人类乳腺癌和子宫癌具有一些共同特征，并指出了共同的机制途径。我们的数据表明，与年龄匹配的对照组相比，仓鼠肾肿瘤中总线粒体 DNA 的拷贝数和核编码线粒体柠檬酸合酶的活性显着降低。由于细胞中有数百个线粒体，并且每个线粒体都有多个线粒体DNA拷贝，因此极小比例的体细胞缺失突变可能不足以导致线粒体基因组容量下降。然而，缺失突变的显着增加或线粒体DNA拷贝数的减少可导致线粒体氧化磷酸化能力降低和能量降低，从而增加对疾病过程的易感性。因此，雌激素诱导的仓鼠肾肿瘤模型可以成为一种有用的啮齿动物致癌模型，以了解 mtDNA 损伤在癌症进展和发展中的作用。 © 2002 Wiley periodicals, Inc. J Biochem Mol Toxicol 16:1–9, 2002； DOI 10.1002/jbt.10017
Mitochondrial DNA (mtDNA) encodes for 13 polypeptides critical for normal functioning of the electron transport chain and damage to mtDNA has been associated with aging, and implicated in several disease processes. Although damage to mtDNA is being implicated in mutagenesis and carcinogenesis, there are limited studies demonstrating the role and extent of mtDNA damage in human or rodent cancers. Using serial dilution and competitive polymerase chain reaction analysis, we have quantitated the amount of total mtDNA and analyzed the extent of mtDNA damage in estrogen‐induced and estrogen‐dependent hamster kidney tumors. The hamster kidney tumor model is a useful and widely investigated rodent model of hormonal carcinogenesis, which shares several characteristics with human breast and uterine cancers, and point to a common mechanistic pathway. Our data indicate a significant decrease in the copy number of total mtDNA and the activity of a nuclear‐encoded mitochondrial enzyme citrate synthase in hamster kidney tumors compared to age‐matched controls. Since there are several hundred mitochondria in a cell and each mitochondrion has multiple copies of mtDNA, a very small percentage of somatic deletion mutation may not be enough to result in a decreased capacity of the mitochondrial genome. However, a significant increase in deletion mutations or a decrease in the mtDNA copy number can result in a decreased oxidative phosphorylation capacity of the mitochondria and decreased energetics, and thus increased susceptibility to the disease process. Therefore, estrogen‐induced hamster kidney tumor model can be a useful rodent model of carcinogenesis to understand the role of mtDNA damage in cancer progression and development. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:1–9, 2002; DOI 10.1002/jbt.10017