title: Metabolic restriction of cancer cells in vitro causes karyotype contraction--an indicator of cancer promotion?
abstract: The metabolism of cultured cancer cells is stimulated by 21% oxygen and generous nutrition, while real tumors grow in oxygen and nutrient-restricted environments. The effect of these contrasted conditions was studied in five hyperploid (54-69) cancer cell lines. When grown under anoxia and in the presence of antioxidant metabolic restrictors, the cell lines quickly reverted to almost normal chromosome numbers (47-49). The stepped withdrawal of oxygen over K562 showed progressive increases in proliferation rate and the acquisition of a stable, stem phenotype. In genetic studies, hyperploid cancer cells adjusted their chromosome numbers up or down to match their micro-environment through rapid mechanisms of endo-reduplication or chromosome loss. These fast reactions may explain the surprising adaptability of tumor cells to oncologic interventions. Furthermore, karyotype contraction may provide a basis for the previously observed carcinogenic influence of the administration of some antioxidants in human populations.
authors.affiliation: InVitroPlus Laboratory, Department of Surgery, Royal Victoria Hospital, Montreal, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Héroux
authors.forename: Igor
authors.initials: I
authors.lastname: Kyrychenko
mesh_terms: D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D043171:Chromosomal Instability; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D010100:Oxygen
references.citation: Life Sci. 2004 Nov 26;76(2):121-35
references.pmid: 15519359
references.citation: Biol Pharm Bull. 2004 Apr;27(4):492-5
references.pmid: 15056853
references.citation: N Engl J Med. 1996 May 2;334(18):1150-5
references.pmid: 8602180
references.citation: Stem Cell Rev Rep. 2011 Jun;7(2):471-7
references.pmid: 21188651
references.citation: Mutat Res. 2005 Jan 6;569(1-2):87-100
references.pmid: 15603754
references.citation: Can J Physiol Pharmacol. 2002 Feb;80(2):103-9
references.pmid: 11934252
references.citation: Cancer Res. 1997 Oct 1;57(19):4183-6
references.pmid: 9331071
references.citation: Int J Biochem Cell Biol. 2010 May;42(5):604-22
references.pmid: 19931409
references.citation: J Biol Chem. 1989 Sep 5;264(25):14885-92
references.pmid: 2768244
references.citation: Nat Rev Mol Cell Biol. 2006 Mar;7(3):211-24
references.pmid: 16496023
references.citation: Cell Cycle. 2010 Aug 15;9(16):3256-76
references.pmid: 20814239
references.citation: Biosci Rep. 2004 Dec;24(6):631-9
references.pmid: 16158200
references.citation: Biochim Biophys Acta. 1999 Oct 18;1472(1-2):206-14
references.pmid: 10572942
references.citation: Cancer Res. 2005 Apr 15;65(8):3171-8
references.pmid: 15833847
references.citation: Circ Res. 2007 Feb 16;100(3):328-41
references.pmid: 17307971
references.citation: Oncogene. 2008 Dec;27 Suppl 2:S43-51
references.pmid: 19956179
references.citation: PLoS One. 2007 Jun 27;2(6):e558
references.pmid: 17593959
references.citation: Am J Pathol. 1999 Jun;154(6):1825-30
references.pmid: 10362807
references.citation: Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):553-68
references.pmid: 15897180
references.citation: Int J Radiat Oncol Biol Phys. 1996 Jul 1;35(4):701-8
references.pmid: 8690636
references.citation: PLoS One. 2009;4(5):e5442
references.pmid: 19421315
references.citation: Leuk Res. 2001 Apr;25(4):313-22
references.pmid: 11248328
references.citation: Tsitologiia. 1988 Nov;30(11):1355-63
references.pmid: 3245098
references.citation: J Physiol. 2006 Jul 1;574(Pt 1):63-71
references.pmid: 16613876
references.citation: Am J Physiol. 1999 Jul;277(1):E1-10
references.pmid: 10409121
references.citation: Nature. 2009 Apr 23;458(7241):1056-60
references.pmid: 19262508
references.citation: Nat Rev Cancer. 2002 Nov;2(11):815-25
references.pmid: 12415252
references.citation: Nat Genet. 2003 Aug;34(4):369-76
references.pmid: 12923544
references.citation: Semin Radiat Oncol. 2009 Apr;19(2):106-11
references.pmid: 19249648
references.citation: Biochim Biophys Acta. 1984 Oct 26;767(1):130-7
references.pmid: 6237687
references.citation: Blood. 1993 Oct 1;82(7):2031-7
references.pmid: 8104535
references.citation: Carcinogenesis. 2011 Mar;32(3):359-67
references.pmid: 21163886
references.citation: Ann N Y Acad Sci. 1994 Nov 17;738:419-20
references.pmid: 7832450
references.citation: J Cell Sci. 2007 Dec 1;120(Pt 23):4155-66
references.pmid: 18032788
references.citation: Br Med J. 1962 Dec 1;2(5317):1431-5
references.pmid: 13978541
references.citation: BMC Med. 2011 May 23;9:62
references.pmid: 21605374
references.citation: Drug Resist Updat. 2007 Feb-Apr;10(1-2):51-8
references.pmid: 17387035
references.citation: J Mol Endocrinol. 2011 Aug 03;47(1):81-97
references.pmid: 21610007
references.citation: Bioessays. 2001 Dec;23(12):1112-9
references.pmid: 11746230
references.citation: Oncogene. 2006 Aug 7;25(34):4675-82
references.pmid: 16892081
references.citation: Cancers (Basel). 2011 Jul 22;3(3):3002-17
references.pmid: 24310356
references.citation: Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):840-8
references.pmid: 11699496
references.citation: Science. 1976 Oct 1;194(4260):23-8
references.pmid: 959840
references.citation: Blood. 1975 Mar;45(3):321-34
references.pmid: 163658
references.citation: Annu Rev Biophys Biomol Struct. 2001;30:23-65
references.pmid: 11340051
references.citation: N Engl J Med. 1994 Apr 14;330(15):1029-35
references.pmid: 8127329
references.citation: Nature. 1998 Dec 17;396(6712):643-9
references.pmid: 9872311
references.citation: J Clin Invest. 2008 May;118(5):1965-73
references.pmid: 18431513
references.citation: Mol Cell Biol. 2009 Jun;29(11):2982-96
references.pmid: 19289494
references.citation: Cancer Metastasis Rev. 1984;3(3):193-222
references.pmid: 6388823
references.citation: Clin Exp Metastasis. 1997 Jan;15(1):19-25
references.pmid: 9009102
references.citation: Cancer Res. 1996 Mar 1;56(5):941-3
references.pmid: 8640781
references.citation: Cancer Lett. 2003 Jul 18;197(1-2):145-50
references.pmid: 12880974
references.citation: Nature. 2004 Nov 18;432(7015):338-41
references.pmid: 15549096
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85
references.pmid: 17712357
references.citation: Cancer Genet Cytogenet. 1990 Jan;44(1):107-18
references.pmid: 2293876
references.citation: JAMA. 2011 Oct 12;306(14):1549-56
references.pmid: 21990298
references.citation: BMC Cancer. 2010 Jul 22;10:388
references.pmid: 20649952
references.citation: Exp Hematol. 2007 Jan;35(1):21-31
references.pmid: 17198870
references.citation: J Natl Cancer Inst. 1953 Aug;14(1):1-43
references.pmid: 13097135
references.citation: Nat Genet. 1998 Sep;20(1):66-9
references.pmid: 9731534
references.citation: Nat Rev Cancer. 2007 Apr;7(4):233-45
references.pmid: 17361217
references.citation: Cancer Res. 1974 Oct;34(10):2615-23
references.pmid: 4137725
references.citation: Cancer Res. 1993 May 1;53(9):2140-6
references.pmid: 8481917
references.citation: Cancer Res. 2006 May 1;66(9):4553-7
references.pmid: 16651403
references.citation: Biochem J. 1999 Jun 15;340 ( Pt 3):621-30
references.pmid: 10359645
references.citation: Genes Dev. 2009 Mar 1;23(5):537-48
references.pmid: 19270154
references.citation: Mol Cell. 2005 Apr 29;18(3):283-93
references.pmid: 15866171
references.citation: Int J Oncol. 2002 Nov;21(5):1041-51
references.pmid: 12370753
references.citation: J Natl Cancer Inst. 2001 Feb 21;93(4):266-76
references.pmid: 11181773
references.citation: Exp Hematol. 1983 Aug;11(7):601-10
references.pmid: 6576909
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Cell Metab. 2011 Jul 6;14(1):131-42
references.pmid: 21723511
references.citation: Cancer Res. 1983 Mar;43(3):1361-4
references.pmid: 6402298