DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice
Tóm tắt
Chronic inflammation induces DNA damage and promotes cell proliferation, thereby increasing the risk of cancer. DNA polymerase κ (Pol κ), involved in translesion DNA synthesis, counteracts mutagenesis induced by inflammation in the colon of mice. In the present study, we examined whether Pol κ suppressed inflammation-induced colon tumorigenesis by treating inactivated Polk knock-in (Polk−/−) mice with dextran sulfate sodium (DSS), an inducer of colon inflammation. Male and female Polk−/− and Polk+/+ mice were administered 2% DSS in drinking water for six consecutive days, succeeded via a recovery period of 16 days, followed by 2% DSS for another two days. DSS treatment strongly induced colitis, and the severity of colitis was higher in Polk−/− mice than in Polk+/+ mice. The mice were sacrificed after 19 weeks from the initiation of the first DSS treatment and subjected to pathological examination and mutation analysis. DSS treatment induced colonic dysplasia, and the multiplicity of dysplasia was higher in Polk−/− mice than in Polk+/+mice. Some of the dysplasias in Polk−/− mice exhibited β-catenin-stained nucleus and/or cytoplasm. Mutation frequencies in the gpt reporter gene were increased by DSS treatment in Polk−/− mice, and were higher than those in Polk+/+ mice. Pol κ suppresses inflammation and inflammation-induced dysplasia as well as inflammation-induced mutagenesis. The possible mechanisms by which Pol κ suppresses colitis- and colitis-induced dysplasia are discussed.
Tài liệu tham khảo
citation_journal_title=Gastroenterology; citation_title=Epidemiology and natural history of inflammatory bowel diseases; citation_author=J Cosnes, C Gower-Rousseau, P Seksik, A Cortot; citation_volume=140; citation_issue=6; citation_publication_date=2011; citation_pages=1785-1794; citation_doi=10.1053/j.gastro.2011.01.055; citation_id=CR1
citation_journal_title=Cancer Lett; citation_title=Chronic ulcerative colitis and colorectal cancer; citation_author=G Rogler; citation_volume=345; citation_issue=2; citation_publication_date=2014; citation_pages=235-241; citation_doi=10.1016/j.canlet.2013.07.032; citation_id=CR2
citation_journal_title=J Clin Invest; citation_title=Inflammation, atrophy, and gastric cancer; citation_author=JG Fox, TC Wang; citation_volume=117; citation_issue=1; citation_publication_date=2007; citation_pages=60-69; citation_doi=10.1172/JCI30111; citation_id=CR3
citation_journal_title=Free Radic Res; citation_title=Chemistry meets biology in colitis-associated carcinogenesis; citation_author=A Mangerich, PC Dedon, JG Fox, SR Tannenbaum, GN Wogan; citation_volume=47; citation_issue=11; citation_publication_date=2013; citation_pages=958-986; citation_doi=10.3109/10715762.2013.832239; citation_id=CR4
citation_journal_title=Nature; citation_title=Inflammation and cancer; citation_author=LM Coussens, Z Werb; citation_volume=420; citation_issue=6917; citation_publication_date=2002; citation_pages=860-867; citation_doi=10.1038/nature01322; citation_id=CR5
citation_journal_title=Front Microbiol; citation_title=The pivotal role of DNA repair in infection mediated-inflammation and Cancer; citation_author=AZ Sahan, TK Hazra, S Das; citation_volume=9; citation_publication_date=2018; citation_pages=663; citation_doi=10.3389/fmicb.2018.00663; citation_id=CR6
citation_journal_title=Biochimie; citation_title=High fidelity and lesion bypass capability of human DNA polymerase delta; citation_author=MW Schmitt, Y Matsumoto, LA Loeb; citation_volume=91; citation_issue=9; citation_publication_date=2009; citation_pages=1163-1172; citation_doi=10.1016/j.biochi.2009.06.007; citation_id=CR7
citation_journal_title=Science; citation_title=Specialized DNA polymerases, cellular survival, and the genesis of mutations; citation_author=EC Friedberg, R Wagner, M Radman; citation_volume=296; citation_issue=5573; citation_publication_date=2002; citation_pages=1627-1630; citation_doi=10.1126/science.1070236; citation_id=CR8
citation_journal_title=Nat Rev Cancer; citation_title=DNA polymerases and cancer; citation_author=SS Lange, K Takata, RD Wood; citation_volume=11; citation_issue=2; citation_publication_date=2011; citation_pages=96-110; citation_doi=10.1038/nrc2998; citation_id=CR9
citation_journal_title=Annu Rev Microbiol; citation_title=Environmental stress and lesion-bypass DNA polymerases; citation_author=T Nohmi; citation_volume=60; citation_publication_date=2006; citation_pages=231-253; citation_doi=10.1146/annurev.micro.60.080805.142238; citation_id=CR10
citation_journal_title=Cell Res; citation_title=The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases; citation_author=SD McCulloch, TA Kunkel; citation_volume=18; citation_issue=1; citation_publication_date=2008; citation_pages=148-161; citation_doi=10.1038/cr.2008.4; citation_id=CR11
citation_journal_title=Annu Rev Biochem; citation_title=Translesion and repair DNA polymerases: diverse structure and mechanism; citation_author=W Yang, Y Gao; citation_volume=87; citation_publication_date=2018; citation_pages=239-261; citation_doi=10.1146/annurev-biochem-062917-012405; citation_id=CR12
citation_journal_title=J Biol Chem; citation_title=Eukaryotic DNA polymerases: proposal for a revised nomenclature; citation_author=PM Burgers, EV Koonin, E Bruford, L Blanco, KC Burtis, MF Christman; citation_volume=276; citation_issue=47; citation_publication_date=2001; citation_pages=43487-43490; citation_doi=10.1074/jbc.R100056200; citation_id=CR13
citation_journal_title=Nat Rev Mol Cell Biol; citation_title=Y-family DNA polymerases and their role in tolerance of cellular DNA damage; citation_author=JE Sale, AR Lehmann, R Woodgate; citation_volume=13; citation_issue=3; citation_publication_date=2012; citation_pages=141-152; citation_doi=10.1038/nrm3289; citation_id=CR14
citation_journal_title=Annu Rev Biochem; citation_title=Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function; citation_author=S Prakash, RE Johnson, L Prakash; citation_volume=74; citation_publication_date=2005; citation_pages=317-353; citation_doi=10.1146/annurev.biochem.74.082803.133250; citation_id=CR15
citation_journal_title=DNA Repair (Amst); citation_title=In vivo evidence that DNA polymerase kappa is responsible for error-free bypass across DNA cross-links induced by mitomycin C; citation_author=A Takeiri, NA Wada, S Motoyama, K Matsuzaki, H Tateishi, K Matsumoto; citation_volume=24; citation_publication_date=2014; citation_pages=113-121; citation_doi=10.1016/j.dnarep.2014.09.002; citation_id=CR16
citation_journal_title=Mutat Res; citation_title=Recent advances in the protocols of transgenic mouse mutation assays; citation_author=T Nohmi, T Suzuki, K Masumura; citation_volume=455; citation_issue=1–2; citation_publication_date=2000; citation_pages=191-215; citation_doi=10.1016/S0027-5107(00)00077-4; citation_id=CR17
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Polκ protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene; citation_author=T Ogi, Y Shinkai, K Tanaka, H Ohmori; citation_volume=99; citation_issue=24; citation_publication_date=2002; citation_pages=15548-15553; citation_doi=10.1073/pnas.222377899; citation_id=CR18
citation_journal_title=Biochemistry; citation_title=The steric gate amino acid tyrosine 112 is required for efficient mismatched-primer extension by human DNA polymerase kappa; citation_author=N Niimi, A Sassa, A Katafuchi, P Gruz, H Fujimoto, RR Bonala; citation_volume=48; citation_issue=20; citation_publication_date=2009; citation_pages=4239-4246; citation_doi=10.1021/bi900153t; citation_id=CR19
citation_journal_title=Biochemistry; citation_title=Translesion synthesis by human DNA polymerase kappa on a DNA template containing a single stereoisomer of dG-(+)- or dG-(-)-anti-N-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene); citation_author=N Suzuki, E Ohashi, A Kolbanovskiy, NE Geacintov, AP Grollman, H Ohmori; citation_volume=41; citation_issue=19; citation_publication_date=2002; citation_pages=6100-6106; citation_doi=10.1021/bi020049c; citation_id=CR20
citation_journal_title=Environ Mol Mutagen; citation_title=Catalytic and non-catalytic roles of DNA polymerase kappa in the protection of human cells against genotoxic stresses; citation_author=Y Kanemaru, T Suzuki, N Niimi, P Gruz, K Matsumoto, N Adachi; citation_volume=56; citation_issue=8; citation_publication_date=2015; citation_pages=650-662; citation_doi=10.1002/em.21961; citation_id=CR21
citation_journal_title=Cancer Sci; citation_title=A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate; citation_author=T Tanaka, H Kohno, R Suzuki, Y Yamada, S Sugie, H Mori; citation_volume=94; citation_issue=11; citation_publication_date=2003; citation_pages=965-973; citation_doi=10.1111/j.1349-7006.2003.tb01386.x; citation_id=CR22
citation_journal_title=Food Chem Toxicol; citation_title=Rapid induction of colonic adenocarcinoma in mice exposed to benzo[a]pyrene and dextran sulfate sodium; citation_author=A Hakura, Y Seki, J Sonoda, S Hosokawa, T Aoki, A Suganuma; citation_volume=49; citation_issue=11; citation_publication_date=2011; citation_pages=2997-3001; citation_doi=10.1016/j.fct.2011.07.057; citation_id=CR23
citation_journal_title=Environ Mol Mutagen; citation_title=DNA polymerase kappa counteracts inflammation-induced mutagenesis in multiple organs of mice; citation_author=A Hakura, H Sui, J Sonoda, T Matsuda, T Nohmi; citation_volume=60; citation_issue=4; citation_publication_date=2019; citation_pages=320-330; citation_doi=10.1002/em.22272; citation_id=CR24
citation_journal_title=Environ Mol Mutagen; citation_title=Limited ability of DNA polymerase kappa to suppress benzo[a]pyrene-induced genotoxicity in vivo; citation_author=K Masumura, N Toyoda-Hokaiwado, N Niimi, P Gruz, NA Wada, A Takeiri; citation_volume=58; citation_issue=9; citation_publication_date=2017; citation_pages=644-653; citation_doi=10.1002/em.22146; citation_id=CR25
citation_journal_title=Nutr Cancer; citation_title=Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays; citation_author=H Mori, F Ohbayashi, I Hirono, T Shimada, GM Williams; citation_volume=6; citation_issue=2; citation_publication_date=1984; citation_pages=92-97; citation_doi=10.1080/01635588509513812; citation_id=CR26
citation_journal_title=J Toxicol Sci; citation_title=Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice; citation_author=T Okamura, Y Ishii, Y Suzuki, T Inoue, M Tasaki, Y Kodama; citation_volume=35; citation_issue=5; citation_publication_date=2010; citation_pages=731-741; citation_doi=10.2131/jts.35.731; citation_id=CR27
citation_journal_title=J Toxicol Pathol; citation_title=Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium; citation_author=J Sonoda, Y Seki, A Hakura, S Hosokawa; citation_volume=28; citation_issue=2; citation_publication_date=2015; citation_pages=109-120; citation_doi=10.1293/tox.2014-0061; citation_id=CR28
citation_journal_title=Hum Pathol; citation_title=Dysplasia and early carcinoma in inflammatory bowel disease and colorectal adenomas; citation_author=RR Pascal; citation_volume=25; citation_issue=11; citation_publication_date=1994; citation_pages=1160-1171; citation_doi=10.1016/0046-8177(94)90032-9; citation_id=CR29
citation_journal_title=Hum Pathol; citation_title=Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications; citation_author=RH Riddell, H Goldman, DF Ransohoff, HD Appelman, CM Fenoglio, RC Haggitt; citation_volume=14; citation_issue=11; citation_publication_date=1983; citation_pages=931-968; citation_doi=10.1016/S0046-8177(83)80175-0; citation_id=CR30
citation_journal_title=Lab Invest; citation_title=Morphogenesis of chemically induced neoplasms of the colon and small intestine in rats; citation_author=JM Ward; citation_volume=30; citation_issue=4; citation_publication_date=1974; citation_pages=505-513; citation_id=CR31
citation_journal_title=Chem Res Toxicol; citation_title=Detection of lipid peroxidation-induced DNA adducts caused by 4-oxo-2(E)-nonenal and 4-oxo-2(E)-hexenal in human autopsy tissues; citation_author=PH Chou, S Kageyama, S Matsuda, K Kanemoto, Y Sasada, M Oka; citation_volume=23; citation_issue=9; citation_publication_date=2010; citation_pages=1442-1448; citation_doi=10.1021/tx100047d; citation_id=CR32
citation_journal_title=Carcinogenesis; citation_title=Mouse models for the study of colon carcinogenesis; citation_author=DW Rosenberg, C Giardina, T Tanaka; citation_volume=30; citation_issue=2; citation_publication_date=2009; citation_pages=183-196; citation_doi=10.1093/carcin/bgn267; citation_id=CR33
citation_journal_title=Front Genet; citation_title=DNA Damage: From Chronic Inflammation to Age-Related Deterioration; citation_author=A Ioannidou, E Goulielmaki, GA Garinis; citation_volume=7; citation_publication_date=2016; citation_pages=187; citation_doi=10.3389/fgene.2016.00187; citation_id=CR34
citation_journal_title=Curr Opin Immunol; citation_title=Chronic inflammation and aging: DNA damage tips the balance; citation_author=MM Cavanagh, CM Weyand, JJ Goronzy; citation_volume=24; citation_issue=4; citation_publication_date=2012; citation_pages=488-493; citation_doi=10.1016/j.coi.2012.04.003; citation_id=CR35
citation_journal_title=Biochemistry; citation_title=1, N6-ethenodeoxyadenosine, a DNA adduct highly mutagenic in mammalian cells; citation_author=GA Pandya, M Moriya; citation_volume=35; citation_issue=35; citation_publication_date=1996; citation_pages=11487-11492; citation_doi=10.1021/bi960170h; citation_id=CR36
citation_journal_title=Genes Environ; citation_title=Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells; citation_author=T Suzuki, H Kamiya; citation_volume=39; citation_publication_date=2017; citation_pages=2; citation_doi=10.1186/s41021-016-0051-y; citation_id=CR37
citation_journal_title=J Biol Chem; citation_title=Translesion DNA synthesis catalyzed by human pol eta and pol kappa across 1, N6-ethenodeoxyadenosine; citation_author=RL Levine, H Miller, A Grollman, E Ohashi, H Ohmori, C Masutani; citation_volume=276; citation_issue=22; citation_publication_date=2001; citation_pages=18717-18721; citation_doi=10.1074/jbc.M102158200; citation_id=CR38
citation_journal_title=DNA Repair (Amst); citation_title=Discrimination against major groove adducts by Y-family polymerases of the DinB subfamily; citation_author=JM Walsh, PJ Ippoliti, EA Ronayne, E Rozners, PJ Beuning; citation_volume=12; citation_issue=9; citation_publication_date=2013; citation_pages=713-722; citation_doi=10.1016/j.dnarep.2013.05.006; citation_id=CR39
citation_journal_title=J Cell Biol; citation_title=DNA damage-induced immune response: Micronuclei provide key platform; citation_author=NO Gekara; citation_volume=216; citation_issue=10; citation_publication_date=2017; citation_pages=2999-3001; citation_doi=10.1083/jcb.201708069; citation_id=CR40
citation_journal_title=Cell; citation_title=Cytoplasmic DNA: sources, sensing, and role in aging and disease; citation_author=KN Miller, SG Victorelli, H Salmonowicz, N Dasgupta, T Liu, JF Passos; citation_volume=184; citation_issue=22; citation_publication_date=2021; citation_pages=5506-5526; citation_doi=10.1016/j.cell.2021.09.034; citation_id=CR41
citation_journal_title=Cell Rep; citation_title=Disruption of DNA polymerase zeta engages an innate immune response; citation_author=SK Martin, J Tomida, RD Wood; citation_volume=34; citation_issue=8; citation_publication_date=2021; citation_pages=108775; citation_doi=10.1016/j.celrep.2021.108775; citation_id=CR42
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Error-prone translesion replication of damaged DNA suppresses skin carcinogenesis by controlling inflammatory hyperplasia; citation_author=A Tsaalbi-Shtylik, JW Verspuy, JG Jansen, H Rebel, LM Carlee, MA Valk; citation_volume=106; citation_issue=51; citation_publication_date=2009; citation_pages=21836-21841; citation_doi=10.1073/pnas.0909507106; citation_id=CR43
citation_journal_title=Genes Environ; citation_title=The in vivo role of Rev1 in mutagenesis and carcinogenesis; citation_author=M Sasatani, EK Zaharieva, K Kamiya; citation_volume=42; citation_publication_date=2020; citation_pages=9; citation_doi=10.1186/s41021-020-0148-1; citation_id=CR44
citation_journal_title=Inflammation; citation_title=Sex Differences in experimentally induced colitis in mice: a role for estrogens; citation_author=J Babickova, L Tothova, E Lengyelova, A Bartonova, J Hodosy, R Gardlik; citation_volume=38; citation_issue=5; citation_publication_date=2015; citation_pages=1996-2006; citation_doi=10.1007/s10753-015-0180-7; citation_id=CR45
citation_journal_title=J Cancer Prev; citation_title=The Effect of sex on the azoxymethane/dextran sulfate sodium-treated mice model of colon Cancer; citation_author=SM Lee, N Kim, HJ Son, JH Park, RH Nam, MH Ham; citation_volume=21; citation_issue=4; citation_publication_date=2016; citation_pages=271-278; citation_doi=10.15430/JCP.2016.21.4.271; citation_id=CR46
citation_journal_title=Chem Res Toxicol; citation_title=Six germline genetic variations impair the translesion synthesis Activity of human DNA polymerase kappa; citation_author=JK Kim, M Yeom, JK Hong, I Song, YS Lee, FP Guengerich; citation_volume=29; citation_issue=10; citation_publication_date=2016; citation_pages=1741-1754; citation_doi=10.1021/acs.chemrestox.6b00244; citation_id=CR47