Department of Human Anatomy and Histology, University of Bari, Italy.
Clin Exp Med. 2011 Sep;11(3):171-9. doi: 10.1007/s10238-010-0118-1. Epub 2010 Nov 11.
The epithelium of the intestinal tract is exposed to a variety of genotoxic agents, both exogenous and endogenous, that can injure nuclear and mitochondrial DNA. DNA damage can be repaired by a series of DNA repair enzymes, while defects in this system will make these cells once more susceptible to malignant transformation or cell death. Recent studies suggest that intestinal bacteria may contribute to induce inflammation in individuals afflicted by inflammatory bowel disease (IBD), increasing the risk of developing colon cancer. Accumulating evidence suggests that Helicobacter organisms are linked to IBD as well as to gastric and colon cancer. Therefore, the focus of this study was to evaluate the effect of lipopolysaccharide (LPS) isolated from Helicobacter on modulating the DNA repair system. We used an in vitro model represented by two colon carcinoma cell lines, the DNA repair-proficient SW480 and the DNA repair-deficient LoVo, and transfected with a UVC-irradiated psV-beta-galactosidase plasmid. We observed that LPS, by upregulating the expression of inducible nitric oxide (NO), leads to an increased NO release, demonstrating that LPS is able to interfere with the DNA repair machinery of intestinal cells, thus increasing the risk of permanent genotoxic effects.
肠道上皮细胞暴露于各种内源性和外源性的遗传毒性物质中，这些物质会损伤核 DNA 和线粒体 DNA。DNA 损伤可以通过一系列 DNA 修复酶来修复，而该系统的缺陷会使这些细胞更容易恶性转化或死亡。最近的研究表明，肠道细菌可能会导致炎症性肠病 (IBD) 患者发生炎症，增加结肠癌的发病风险。越来越多的证据表明，幽门螺杆菌与 IBD 以及胃癌和结肠癌有关。因此，本研究的重点是评估从幽门螺杆菌中分离出的脂多糖 (LPS) 对调节 DNA 修复系统的影响。我们使用了由两个结肠癌细胞系 SW480 和 DNA 修复缺陷型 LoVo 组成的体外模型，并转染了经 UVC 照射的 psV-β-半乳糖苷酶质粒。我们观察到 LPS 通过上调诱导型一氧化氮合酶 (iNOS) 的表达，导致一氧化氮 (NO) 释放增加，表明 LPS 能够干扰肠道细胞的 DNA 修复机制，从而增加永久性遗传毒性作用的风险。
