Machado Ana Manuel Dantas, Figueiredo Céu, Seruca Raquel, Rasmussen Lene Juel
Department of Science, Systems and Models, University of Roskilde, Denmark.
Biochim Biophys Acta. 2010 Aug;1806(1):58-65. doi: 10.1016/j.bbcan.2010.01.007. Epub 2010 Feb 1.
The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric carcinogenesis by at least three different mechanisms: (1) a combination of increased endogenous DNA damage and decreased repair activities, (2) induction of mutations in the mitochondrial DNA, and (3) generation of a transient mutator phenotype that induces mutations in the nuclear genome.
幽门螺杆菌与胃癌相关这一发现引发了众多研究，这些研究旨在探究幽门螺杆菌诱导癌变的机制。除了重要的DNA修复途径受损外，胃癌在核DNA和线粒体DNA中均表现出基因不稳定。因此，本综述重点阐述了幽门螺杆菌感染对宿主细胞DNA完整性的影响。通过下调主要的DNA修复途径，幽门螺杆菌感染有可能产生突变。此外，幽门螺杆菌感染可诱导宿主DNA发生直接变化，如氧化损伤、甲基化、染色体不稳定、微卫星不稳定和突变。有趣的是，幽门螺杆菌感染会导致核DNA和线粒体DNA出现基因不稳定。基于所综述的文献，我们得出结论：幽门螺杆菌感染至少通过三种不同机制促进胃癌发生：（1）内源性DNA损伤增加与修复活性降低相结合；（2）诱导线粒体DNA突变；（3）产生一种短暂的诱变表型，该表型可诱导核基因组发生突变。
