title: Ambient oxygen promotes tumorigenesis.
abstract: 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.
authors: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Ho Joong
authors: HJ
authors: Sung
authors: Wenzhe
authors: W
authors: Ma
authors: Matthew F
authors: MF
authors: Starost
authors: Cory U
authors: CU
authors: Lago
authors: Philip K
authors: PK
authors: Lim
authors: Michael N
authors: MN
authors: Sack
authors: Ju-Gyeong
authors: JG
authors: Kang
authors: Ping-yuan
authors: PY
authors: Wang
authors: Paul M
authors: PM
authors: Hwang
references: Nat Cell Biol. 2003 Aug;5(8):741-7
references: 12855956
references: J Reprod Fertil. 1993 Nov;99(2):673-9
references: 8107053
references: Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L998-L1006
references: 18344416
references: Nature. 1977 Jun 2;267(5610):423-5
references: 876356
references: Radiat Res. 1987 Nov;112(2):381-90
references: 3685264
references: PLoS One. 2009;4(2):e4630
references: 19247485
references: Pediatrics. 2010 Aug;126(2):270-6
references: 20643723
references: Endocrinology. 2004 Oct;145(10):4667-76
references: 15231693
references: Mol Cell Biol. 1998 Jun;18(6):3495-501
references: 9584189
references: Cell. 2008 Jan 25;132(2):171-6
references: 18243090
references: J Pediatr. 2005 Jul;147(1):27-31
references: 16027689
references: Cancer Res. 1989 Dec 1;49(23):6449-65
references: 2684393
references: Comp Med. 2006 Feb;56(1):17-22
references: 16521855
references: J Physiol. 2002 Feb 1;538(Pt 3):985-94
references: 11826181
references: J Clin Invest. 2009 Apr;119(4):865-75
references: 19307731
references: Nature. 2007 Aug 16;448(7155):767-74
references: 17700693
references: Science. 1992 May 1;256(5057):668-70
references: 1350108
references: Cell. 2006 Dec 15;127(6):1109-22
references: 17112576
references: Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3423-8
references: 15728378
references: Blood. 2007 Oct 15;110(8):3056-63
references: 17595331
references: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7
references: 10318916
references: Science. 2010 Jul 2;329(5987):72-5
references: 20466884
references: Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2533-44
references: 11356608
references: Semin Cancer Biol. 2009 Feb;19(1):32-41
references: 19101635
references: PLoS Biol. 2007 May;5(5):e110
references: 17472436
references: J Sports Sci Med. 2008 Sep 01;7(3):344-9
references: 24149901
references: Science. 1998 Nov 20;282(5393):1497-501
references: 9822382
references: Cell. 1990 Jun 1;61(5):759-67
references: 2188735
references: Science. 2002 Jul 26;297(5581):565-9
references: 12142527
references: N Engl J Med. 2000 Jun 29;342(26):1960-8
references: 10874065
references: Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L87-97
references: 12959929
references: Cancer Cell. 2006 Feb;9(2):109-20
references: 16473278
references: Nat Commun. 2010 Apr 12;1:5
references: 20975668
references: Mayo Clin Proc. 2008 Jan;83(1):23-34
references: 18173999
references: J Exp Biol. 1998 Apr;201(Pt 8):1243-54
references: 9510535
references: Cancer Res. 1986 Apr;46(4 Pt 2):1994-2000
references: 3948176
references: Cancer Cell. 2007 Sep;12(3):230-8
references: 17785204
references: BMC Cancer. 2007 Jan 30;7:23
references: 17263869
references: Cell. 2006 Oct 20;127(2):397-408
references: 17055439
references: Cancer Res. 1994 Nov 15;54(22):5947-52
references: 7954427
references: Science. 1995 Oct 13;270(5234):296-9
references: 7569979
references: Mol Carcinog. 2005 Sep;44(1):31-41
references: 15937958
references: Nature. 2003 Jul 31;424(6948):561-5
references: 12891360
references: Nat Med. 2005 Dec;11(12):1306-13
references: 16286925
references: Nature. 2009 May 21;459(7245):387-392
references: 19404261
references: Mol Cell Biol. 2010 Oct;30(19):4595-603
references: 20679489
references: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1093-8
references: 19144918
references: Oncogene. 2010 Feb 4;29(5):625-34
references: 19946328
references: Clin Cancer Res. 2008 Dec 15;14(24):8094-101
references: 19073969
references: Curr Biol. 1994 Jan 1;4(1):1-7
references: 7922305
references: Nature. 1978 Aug 10;274(5671):606-7
references: 353565