Bancroft Laura K, Lupton Joanne R, Davidson Laurie A, Taddeo Stella S, Murphy Mary E, Carroll Raymond J, Chapkin Robert S
Molecular and Cell Biology Group, Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471, USA.
Free Radic Biol Med. 2003 Jul 15;35(2):149-59. doi: 10.1016/s0891-5849(03)00240-5.
Prolonged generation of reactive oxygen species by inflammatory mediators can induce oxidative DNA damage (8-oxodG formation), potentially resulting in intestinal tumorigenesis. Fish oil (FO), compared to corn oil (CO), has been shown to downregulate inflammation and upregulate apoptosis targeted at damaged cells. We hypothesized FO could protect the intestine against 8-oxodG formation during dextran sodium sulfate- (DSS-) induced inflammation. We provided 60 rats with FO- or CO-supplemented diets for 2 weeks with or without 3% DSS in drinking water for 48 h. Half the treated rats received 48 additional h of untreated water before termination. Due to DSS treatment, the intestinal epithelium had higher levels of 8-oxodG (p =.04), induction of repair enzyme OGG1 mRNA (p =.02), and higher levels of apoptosis at the top of colonic crypts (p =.01) and in surface cells (p <.0001). FO-fed rats, compared to CO, had lower levels of 8-oxodG (p =.05) and increased apoptosis (p =.04) in the upper crypt region; however, FO had no significant effect on OGG1 mRNA. We conclude that FO protects intestinal cells against oxidative DNA damage in part via deletion mechanisms.
炎症介质长时间产生活性氧会诱导氧化性DNA损伤（8-氧代脱氧鸟苷形成），这可能会导致肠道肿瘤发生。与玉米油（CO）相比，鱼油（FO）已被证明可下调炎症反应，并上调针对受损细胞的凋亡。我们假设鱼油可以在葡聚糖硫酸钠（DSS）诱导的炎症过程中保护肠道免受8-氧代脱氧鸟苷的形成。我们给60只大鼠提供富含鱼油或玉米油的饮食2周，同时在饮用水中添加或不添加3%的DSS，持续48小时。一半接受治疗的大鼠在处死前再接受48小时的无处理水。由于DSS处理，肠上皮细胞的8-氧代脱氧鸟苷水平更高（p = 0.04），修复酶OGG1 mRNA的诱导水平更高（p = 0.02），结肠隐窝顶部（p = 0.01）和表面细胞（p < 0.0001）的凋亡水平更高。与喂食玉米油的大鼠相比，喂食鱼油的大鼠在上部隐窝区域的8-氧代脱氧鸟苷水平更低（p = 0.05），凋亡增加（p = 0.04）；然而，鱼油对OGG1 mRNA没有显著影响。我们得出结论，鱼油部分通过缺失机制保护肠道细胞免受氧化性DNA损伤。
