title: Mobilization of LINE-1 in irradiated mammary gland tissue may potentially contribute to low dose radiation-induced genomic instability.
abstract: It is known that cellular stresses such as ionizing radiation activate LINE-1 (long interspersed nuclear element type 1, L1), but the molecular mechanisms of LINE-1 activation have not been fully elucidated. There is a possibility that DNA methylation changes induced by genotoxic stresses might contribute to LINE-1 activation in mammalian cells. L1 insertions usually cause major genomic rearrangements, such as deletions, transductions, the intrachromosomal homologous recombination between L1s, and the generation of pseudogenes, which could lead to genomic instability. The purpose of this study was to evaluate the effects of low and high doses of ionizing radiation on the DNA methylation status of LINE-1 transposable elements in rat mammary glands. Here we describe radiation-induced hypomethylation and activation of LINE-1 ORF1 in rat mammary gland tissues. We show that radiation exposure has also led to the translation of the LINE-1 element, whereby the 148 kDa LINE-1 protein level was increased 96 hours after treatment with a low dose and low energy level radiation and remained elevated for 24 weeks after treatment. The mobilization of LINE-1 in irradiated tissue may potentially contribute to genomic instability. The observed activation of mobile elements in response to radiation exposure is consistently discussed as a plausible mechanism of cancer etiology and development.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
authors.forename: Lidia
authors.initials: L
authors.lastname: Luzhna
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Ilnytskyy
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
keywords: LINE-1; c-myc; ionizing radiation; mammary gland
references.citation: Cell. 1996 Nov 29;87(5):905-16
references.pmid: 8945517
references.citation: Am J Pharmacogenomics. 2002;2(1):25-35
references.pmid: 12083952
references.citation: Cell. 2002 Aug 9;110(3):315-25
references.pmid: 12176319
references.citation: Gene. 1997 Apr 21;189(2):227-34
references.pmid: 9168132
references.citation: Oncotarget. 2013 Nov;4(11):1882-93
references.pmid: 24231191
references.citation: J Virol. 2013 Dec;87(24):13307-20
references.pmid: 24089548
references.citation: DNA Cell Biol. 2012 Sep;31(9):1458-67
references.pmid: 22845795
references.citation: Cancer Res. 2001 May 15;61(10):4238-43
references.pmid: 11358850
references.citation: Trends Ecol Evol. 2000 Mar;15(3):95-99
references.pmid: 10675923
references.citation: Carcinogenesis. 2014 Feb;35(2):333-8
references.pmid: 24130171
references.citation: Mol Carcinog. 2007 Mar;46(3):187-97
references.pmid: 17219426
references.citation: Cancer Res. 1992 Feb 1;52(3):643-5
references.pmid: 1310068
references.citation: Annu Rev Genet. 2001;35:501-38
references.pmid: 11700292
references.citation: Yeast. 2005 Apr 30;22(6):441-55
references.pmid: 15849797
references.citation: Nucleic Acids Res. 1997 Jun 15;25(12):2532-4
references.pmid: 9171110
references.citation: J Biol Chem. 2004 Jun 25;279(26):27753-63
references.pmid: 15056671
references.citation: J Biomed Biotechnol. 2006;2006(1):45621
references.pmid: 16877816
references.citation: Gene. 2012 Dec 10;511(1):46-53
references.pmid: 22982412
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5280-5
references.pmid: 12682288
references.citation: Cell. 2002 Aug 9;110(3):327-38
references.pmid: 12176320
references.citation: Science. 1991 Dec 20;254(5039):1808-10
references.pmid: 1722352
references.citation: Carcinogenesis. 2007 Aug;28(8):1831-8
references.pmid: 17347136
references.citation: FEBS Lett. 2007 Jun 26;581(16):2877-82
references.pmid: 17560999
references.citation: Anticancer Res. 1992 Mar-Apr;12(2):559-63
references.pmid: 1580572
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(18):6990-4
references.pmid: 1698287
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Cell. 1996 Nov 29;87(5):917-27
references.pmid: 8945518
references.citation: Carcinogenesis. 2000 Mar;21(3):397-404
references.pmid: 10688860
references.citation: Nucleic Acids Res. 2006 Feb 28;34(4):1196-204
references.pmid: 16507671
references.citation: Ann N Y Acad Sci. 2008 Aug;1137:171-4
references.pmid: 18837943
references.citation: Oncogene. 1992 Mar;7(3):507-10
references.pmid: 1312702
references.citation: J Natl Cancer Inst. 2005 Mar 16;97(6):406-7
references.pmid: 15769997
references.citation: Cell. 2002 Aug 9;110(3):277-80
references.pmid: 12176313
references.citation: Cancer Res. 2006 Mar 1;66(5):2616-20
references.pmid: 16510580
references.citation: Prostate. 1999 May 15;39(3):166-74
references.pmid: 10334105
references.citation: Nucleic Acids Res. 2005 Feb 08;33(3):846-56
references.pmid: 15701756
references.citation: Oncogene. 2005 Nov 3;24(48):7213-23
references.pmid: 16170379
references.citation: Cancer. 1994 May 1;73(9):2333-6
references.pmid: 8168038
references.citation: Mol Cancer. 2006 Nov 02;5(1):55
references.pmid: 17081305
references.citation: Cancer Cell Int. 2006 May 02;6:13
references.pmid: 16670018
references.citation: Cancer Biol Ther. 2006 Jan;5(1):65-70
references.pmid: 16322686
references.citation: Nature. 1988 May 5;333(6168):87-90
references.pmid: 2834650
references.citation: EMBO J. 1996 Feb 1;15(3):630-9
references.pmid: 8599946
references.citation: Nucleic Acids Res. 2008 Feb;36(2):648-65
references.pmid: 18073200
references.citation: Mol Cell Biol. 2007 Sep;27(18):6469-83
references.pmid: 17562864
references.citation: Mob DNA. 2010 Oct 27;1(1):22
references.pmid: 20979631
references.citation: Nucleic Acids Res. 2003 Aug 1;31(15):4385-90
references.pmid: 12888497
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Mol Cell Biol. 1995 Jul;15(7):3882-91
references.pmid: 7540721