Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients
Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is pro...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2473 |
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| author | Pavel Vodicka Marketa Urbanova Pavol Makovicky Kristyna Tomasova Michal Kroupa Rudolf Stetina Alena Opattova Klara Kostovcikova Anna Siskova Michaela Schneiderova Veronika Vymetalkova Ludmila Vodickova |
| author_facet | Pavel Vodicka Marketa Urbanova Pavol Makovicky Kristyna Tomasova Michal Kroupa Rudolf Stetina Alena Opattova Klara Kostovcikova Anna Siskova Michaela Schneiderova Veronika Vymetalkova Ludmila Vodickova |
| author_sort | Pavel Vodicka |
| collection | DOAJ |
| description | Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy. |
| first_indexed | 2024-03-10T20:43:07Z |
| format | Article |
| id | doaj.art-975e3a4273b44b248fc1687c4e478c17 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:43:07Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-975e3a4273b44b248fc1687c4e478c172023-11-19T20:32:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217247310.3390/ijms21072473Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer PatientsPavel Vodicka0Marketa Urbanova1Pavol Makovicky2Kristyna Tomasova3Michal Kroupa4Rudolf Stetina5Alena Opattova6Klara Kostovcikova7Anna Siskova8Michaela Schneiderova9Veronika Vymetalkova10Ludmila Vodickova11Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00 Prague, Czech RepublicDepartment of Biology, Faculty of Education, J Selye University, Bratislavska 3322, 945 01 Komarno, SlovakiaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Surgery, University Hospital Kralovske Vinohrady in Prague, Third Medical Faculty, Charles University, Ruska 87, 100 00 Prague, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicOxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.https://www.mdpi.com/1422-0067/21/7/2473oxidative DNA damageDNA repairbase excision repair (BER)glycosylasescolorectal cancer |
| spellingShingle | Pavel Vodicka Marketa Urbanova Pavol Makovicky Kristyna Tomasova Michal Kroupa Rudolf Stetina Alena Opattova Klara Kostovcikova Anna Siskova Michaela Schneiderova Veronika Vymetalkova Ludmila Vodickova Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients International Journal of Molecular Sciences oxidative DNA damage DNA repair base excision repair (BER)glycosylases colorectal cancer |
| title | Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients |
| title_full | Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients |
| title_fullStr | Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients |
| title_full_unstemmed | Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients |
| title_short | Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients |
| title_sort | oxidative damage in sporadic colorectal cancer molecular mapping of base excision repair glycosylases in colorectal cancer patients |
| topic | oxidative DNA damage DNA repair base excision repair (BER)glycosylases colorectal cancer |
| url | https://www.mdpi.com/1422-0067/21/7/2473 |
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