Lipopolysaccharide (LPS) of helicobacter modulates cellular DNA repair systems in intestinal cells.
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.
Department of Human Anatomy and Histology, University of Bari, Italy.
Pasqua
P
Cavallo
Antonia
A
Cianciulli
Vincenzo
V
Mitolo
Maria Antonietta
MA
Panaro
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases; D007422:Intestines / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000096:biosynthesis* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010957:Plasmids; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D008070:Lipopolysaccharides; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D004247:DNA; D052247:Nitric Oxide Synthase Type II