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DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice.
Hakura, Atsushi; Sui, Hajime; Seki, Yuki; Sonoda, Jiro; Yoshida, Yusaku; Takagi, Hisayoshi; Yokose, Shigeo; Matsuda, Tomonari; Asakura, Shoji; Nohmi, Takehiko.
Afiliación
  • Hakura A; Global Drug Safety, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-Shi, Ibaraki, 300-2635, Japan. a-hakura@hhc.eisai.co.jp.
  • Sui H; Division of Safety Testing, Food and Drug Safety Center, Hatano Research Institute, Hadano, Kanagawa, 257-0025, Japan.
  • Seki Y; Global Drug Safety, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-Shi, Ibaraki, 300-2635, Japan.
  • Sonoda J; Global Drug Safety, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-Shi, Ibaraki, 300-2635, Japan.
  • Yoshida Y; Present Address: Operations Department, Global Safety HQS, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-Ku, Tokyo, 112-8088, Japan.
  • Takagi H; Biotechnical Center, Japan SLC, Inc., 3-5-1 Aoihigashi, Naka-Ku, Hamamatsu-Shi, Shizuoka, 433-8114, Japan.
  • Yokose S; Biotechnical Center, Japan SLC, Inc., 3-5-1 Aoihigashi, Naka-Ku, Hamamatsu-Shi, Shizuoka, 433-8114, Japan.
  • Matsuda T; Biotechnical Center, Japan SLC, Inc., 3-5-1 Aoihigashi, Naka-Ku, Hamamatsu-Shi, Shizuoka, 433-8114, Japan.
  • Asakura S; Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, 520-0811, Japan.
  • Nohmi T; Global Drug Safety, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-Shi, Ibaraki, 300-2635, Japan.
Genes Environ ; 45(1): 15, 2023 Apr 22.
Article en En | MEDLINE | ID: mdl-37087526
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 ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Genes Environ Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Genes Environ Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido