慢性炎症会引起DNA损伤并促进细胞增殖，从而增加患癌风险。DNA聚合酶κ（Pol κ），参与跨损伤DNA合成，对抗小鼠结肠炎症引起的突变。在本研究中，我们检查了Pol κ是否通过治疗失活的Polk插入（Polk-/-）小鼠，使用右旋糖酐硫酸钠（DSS）来抑制炎症诱导的结肠肿瘤发生。给雄性和雌性Polk-/-和Polk+/+小鼠连续六天口服2%的DSS，随后休息16天，然后再连续两天口服2%的DSS。DSS处理可以强烈诱导结肠炎症，Polk-/-小鼠的炎症严重程度比Polk+/+小鼠更高。在第一次DSS处理后的19周后，将小鼠牺牲并进行病理检查和突变分析。DSS处理会诱导结肠异型增生，Polk-/-小鼠的异型增生多样性高于Polk+/+小鼠。Polk-/-小鼠的一些异型增生表现为β-连环蛋白染色的细胞核和/或细胞质。DSS处理使Polk-/-小鼠的gpt报告基因突变频率增加，高于Polk+/+小鼠。Pol κ抑制炎症和炎症引起的异型增生以及炎症诱导的突变。讨论了Pol κ抑制结肠炎症和结肠炎症引起的异型增生的可能机制。©2023年，作者。

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.© 2023. The Author(s).