| Autor: |
Atsushi Hakura, Hajime Sui, Yuki Seki, Jiro Sonoda, Yusaku Yoshida, Hisayoshi Takagi, Shigeo Yokose, Tomonari Matsuda, Shoji Asakura, Takehiko Nohmi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Genes and Environment, Vol 45, Iss 1, Pp 1-13 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1880-7062 |
| DOI: |
10.1186/s41021-023-00272-7 |
| Popis: |
Abstract Background 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. Results 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. Conclusions 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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