Gastric cancer is one of the most common and often fatal cancers: Every third cancer death is due to gastric carcinoma. The main risk factor for the development of gastric cancer is the chronic infection of the gastric mucosa with the bacterium Helicobacter pylori. Since this bacterium was discovered in 1983, scientists have been puzzling over the molecular mechanisms triggering carcinogenesis. Now, several research teams headed by Prof. Anne Müller and Prof. Massimo Lopes from the Institute of Molecular Cancer Research at the University of Zurich have demonstrated how Helicobacter pylori harms human and animal host cells in in vitro experiments. The study published in the science journal PNAS shows that the infection in the host cell leads to DNA breaks in both strands of the double helix.
Degree of damage depends on duration of infection
Müller, Lopes and their teams also show that the frequency of the double-strand breaks depends on the intensity and duration of the infection. Caused by the infection with Helicobacter pylori, the breaks trigger the usual DNA damage signaling and repair mechanisms. If the bacterium is killed off with antibiotics within a few hours of infection, most of the breaks can actually be repaired successfully. Prolonged infections that imitate the conditions in the chronically infected host, however, exhaust the cell’s repair response and the dangerous double-strand breaks can no longer or only imprecisely be repaired, causing genetic mutations or the death of the cell. The new findings are in agreement with the previously described genomic instability of gastric cancer cells and will be important for a better understanding of the pathological mechanisms promoting gastric carcinogenesis.
The research was also funded with contributions from the Swiss National Science Foundation, the Schweizer Krebsliga (Swiss Cancer Society) and the Research Credit of the University of Zurich.
Isabella M. Toller, Kai Neelsen, Martin Steger, Mara L. Hartung, Michael O. Hottiger, Manuel Stucki, Behnam Kalali, Markus Gerhard, Alessandro A. Sartori, Massimo Lopes and Anne Müller: The Carcinogenic Bacterial Pathogen Helicobacter pylori triggers DNA Double Strand Breaks and a DNA Damage Response in its Host Cells", IN: PNAS Early Edition, doi: 10.1073/pnas.1100959108