BACKGROUND We investigated the influence of hypoxia on the concentration of mitochondrial and nuclear cell-free DNA (McfDNA and NcfDNA, respectively). METHOD By an ultra-sensitive quantitative PCR-based assay, McfDNA and NcfDNA were measured in the supernatants of different colorectal cell lines, and in the plasma of C57/Bl6 mice engrafted with TC1 tumour cells, in normoxic or hypoxic conditions. RESULTS Our data when setting cell culture conditions highlighted the higher stability of McfDNA as compared to NcfDNA and revealed that cancer cells released amounts of nuclear DNA equivalent to the mass of a chromosome over a 6-h duration of incubation. In cell model, hypoxia induced a great increase in NcfDNA and McfDNA concentrations within the first 24 h. After this period, cfDNA total concentrations remained stable in hypoxia consecutive to a decrease of nuclear DNA release, and noteworthy, to a complete inhibition of daily mitochondrial DNA release. In TC1-engrafted mice submitted to intermittent hypoxia, plasma NcfDNA levels are much higher than in mice bred in normoxia, unlike plasma McfDNA concentration that is not impacted by hypoxia. CONCLUSION This study suggests that hypoxia negatively modulates nuclear and, particularly, mitochondrial DNA releases in long-term hypoxia, and revealed that the underlying mechanisms are differently regulated.

中文翻译：

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缺氧以不同方式调节线粒体和核 DNA 的释放。

背景我们研究了缺氧对线粒体和核细胞游离 DNA（分别为 McfDNA 和 NcfDNA）浓度的影响。方法 通过基于超灵敏定量 PCR 的测定，在常氧或低氧条件下测量不同结直肠细胞系的上清液以及移植了 TC1 肿瘤细胞的 C57/Bl6 小鼠血浆中的 McfDNA 和 NcfDNA。结果我们在设定细胞培养条件时的数据强调了与 NcfDNA 相比，McfDNA 具有更高的稳定性，并表明癌细胞在 6 小时的孵育时间内释放出相当于染色体质量的核 DNA。在细胞模型中，缺氧导致 NcfDNA 和 McfDNA 浓度在前 24 小时内大幅增加。此后，随着核 DNA 释放的减少，cfDNA 总浓度在缺氧中保持稳定，值得注意的是，日常线粒体 DNA 释放被完全抑制。在接受间歇性缺氧的 TC1 移植小鼠中，血浆 NcfDNA 水平远高于在常氧条件下饲养的小鼠，这与不受缺氧影响的血浆 McfDNA 浓度不同。结论 这项研究表明，长期缺氧会对细胞核、尤其是线粒体 DNA 的释放产生负面影响，并揭示了潜在的机制受到不同的调节。