Jolly Arthur J, Wild Christopher P, Hardie Laura J
Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, UK.
Free Radic Res. 2009 Mar;43(3):234-40. doi: 10.1080/10715760802684211. Epub 2009 Jan 20.
Patients with chronic gastro-oesophageal reflux disease experience the reflux of acid and bile into the distal oesophagus. The secondary bile salt sodium deoxycholate (NDC) is implicated in the induction of mucosal injury during reflux episodes. This study hypothesized that NDC damages DNA in oesophageal cells by an oxidative mechanism. In the oesophageal cell line HET1-A, increased production of nitric oxide (NO) was measured in NDC-treated cells. Protection from DNA strand breaks induced by NDC (10 microm) was observed in cells coincubated with the nitric oxide scavenger C-PTIO (p<0.012) or pre-incubated with the NO synthase inhibitor L-NAME (p<0.009) or the NFkappaB inhibitor, TPCK (p<0.036). Collectively these data implicate the involvement of NFkappaB and nitric oxide synthase in the DNA damage induced by NDC in oesophageal cells. In conclusion, NDC-driven NO production may play an important role in inducing DNA damage during episodes of gastro-oesophageal reflux and thereby contribute to reflux-related carcinogenesis.
患有慢性胃食管反流病的患者会经历胃酸和胆汁反流至食管远端。次级胆盐脱氧胆酸钠（NDC）与反流发作期间黏膜损伤的诱导有关。本研究假设NDC通过氧化机制损伤食管细胞中的DNA。在食管细胞系HET1-A中，经NDC处理的细胞中一氧化氮（NO）的产生增加。在与一氧化氮清除剂C-PTIO共同孵育的细胞中（p<0.012），或与NO合酶抑制剂L-NAME预孵育的细胞中（p<0.009），或与NFκB抑制剂TPCK预孵育的细胞中（p<0.036），观察到对NDC（10微摩尔）诱导的DNA链断裂有保护作用。这些数据共同表明NFκB和一氧化氮合酶参与了NDC诱导的食管细胞DNA损伤。总之，NDC驱动的NO产生可能在胃食管反流发作期间诱导DNA损伤中起重要作用，从而导致与反流相关的致癌作用。
