{"title":"叶酸缺乏增强了胆汁酸在人结肠和肝细胞中的体外遗传毒性。","authors":"Jianfei Li, Cheng Zhang, Lingzhi Li, Xueqin Hu, Yizhen Jia, Yanan Huang, Ting Lyu, Xu Wang, Xihan Guo","doi":"10.1093/mutage/geab041","DOIUrl":null,"url":null,"abstract":"<p><p>Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"37 1","pages":"34-43"},"PeriodicalIF":2.5000,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"Folate deficiency enhances the in vitro genotoxicity of bile acids in human colon and liver cells.\",\"authors\":\"Jianfei Li, Cheng Zhang, Lingzhi Li, Xueqin Hu, Yizhen Jia, Yanan Huang, Ting Lyu, Xu Wang, Xihan Guo\",\"doi\":\"10.1093/mutage/geab041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).</p>\",\"PeriodicalId\":18889,\"journal\":{\"name\":\"Mutagenesis\",\"volume\":\"37 1\",\"pages\":\"34-43\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2022-04-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutagenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/mutage/geab041\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mutage/geab041","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 3
摘要
肥胖受试者具有较高的基因毒性应激基线,但其潜在机制尚不清楚。鉴于肥胖与高胆汁酸(BA)和低叶酸有关,我们旨在确定叶酸缺乏或补充对人类结肠和肝细胞中BA的遗传毒性和细胞毒性的相互作用。NCM460和L-02细胞在叶酸缺乏(22.6 nM)和叶酸充足(2260 nM)的Roswell Park Memorial Institute (RPMI)-1640培养基中分别添加或不添加50 μM脱氧胆酸(DCA)或石胆酸(LCA)培养7天。将这些细胞分别在添加叶酸(5.65、11.3和22.6 μM)和添加200 μM DCA或LCA的标准(2.26 μM)培养基中培养7 d。采用细胞动力学阻断微核细胞组法测定遗传毒性和细胞毒性。结果表明,在叶酸充足的条件下,50 μM DCA或LCA均能显著提高NCM460和L-02细胞的微核(MN)率。叶酸缺乏进一步增强了50 μM DCA或LCA诱导mn的效果。有趣的是,在NCM460和L-02细胞中,补充叶酸具有剂量依赖性,可显著降低200 μM DCA或LCA诱导的MN、核质桥、核芽、凋亡和坏死率。由此可见,叶酸缺乏可加重中等BA (50 μM)的遗传毒性,叶酸补充可有效保护细胞免受高BA (200 μM)的遗传毒性和细胞毒性。
Folate deficiency enhances the in vitro genotoxicity of bile acids in human colon and liver cells.
Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).
期刊介绍:
Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.