Ambient oxygen promotes tumorigenesis.

Ambient oxygen promotes tumorigenesis.
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DOI:
10.1371/journal.pone.0019785
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发表时间:
2011-05-12
期刊:
影响因子:
3.7
通讯作者:
Hwang PM
Hwang PM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sung HJ;Ma W;Starost MF;Lago CU;Lim PK;Sack MN;Kang JG;Wang PY;Hwang PM

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氧是氧化应激的重要因素,已被证明是细菌中的诱变剂。虽然众所周知,环境中的氧气也可以导致培养的哺乳动物细胞的基因组不稳定,但它在生物水平上对新生肿瘤发生的影响尚不清楚。在这里,我们报告了通过减少环境中的氧气暴露,∼使P53−/−小鼠的中位无肿瘤生存时间增加了50%。在胸腺中,减少氧气暴露降低了氧化dna损伤和RAG重组酶的水平,这两者都被认为可以促进p53−/−小鼠的淋巴肿大。在另外两个涉及APC肿瘤抑制基因和化学致癌的癌症模型中,氧进一步被证明与基因组不稳定性有关。总之,这些观察结果是第一个直接测试环境氧对新生肿瘤形成影响的报告,并提供了重要的生理学证据,证明了环境氧在增加体内基因组不稳定性方面的关键作用。
Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53−/− mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53−/− mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo.
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