Bacterium Associated with Stomach Cancer Directly Damages DNA ► NCI Cancer Bulletin for September 20, 2011 - National Cancer Institute

NCI Cancer Bulletin for September 20, 2011 - National Cancer Institute: Bacterium Associated with Stomach Cancer Directly Damages DNA

A new study helps explain how infection with the stomach bacterium Helicobacter pylori, the strongest known risk factor for gastric (stomach) cancer, may lead to cancer. Researchers have found that H. pylori infection triggers breaks in both strands of the DNA double helix in the nucleus of gastric epithelial cells. These DNA double-strand breaks activate the cells’ machinery for repairing DNA damage, but prolonged H. pylori infection overloads this machinery, which could lead to mutations involved in gastric cancer development.

Drs. Anne Müller and Massimo Lopes of the University of Zurich and their colleagues reported the findings online September 6 in Proceedings of the National Academy of Sciences.

“Human biopsies from infected individuals reveal higher mutation rates of gastric mucosal cells, and results from animal models suggested the same,” Dr. Müller wrote in an e-mail. “But very little is known regarding the mechanism” that causes these mutations.

Using techniques that analyze DNA integrity, the researchers showed that exposing laboratory-grown cells to H. pylori caused DNA double-strand breaks in human gastric cancer cells and in normal mouse gastric epithelial cells. The frequency of double-strand breaks—the most harmful lesions a cell can encounter, according to the authors—depended on the intensity and duration of exposure.

The researchers also showed that DNA damage depends on direct contact of live H. pylori bacteria with their host cells and is not caused by factors such as toxins that these bacteria secrete.

“Our study is one of the few suggesting direct DNA damage as the cause for mutations,” Dr. Müller noted. Other studies have suggested that chronic H. pylori infection and resulting inflammation lead indirectly to DNA damage by triggering the production of chemicals known as reactive oxygen species, which cause oxidation of DNA, but this study ruled out a role for oxidation.

Although most DNA breaks were repaired efficiently by the cell when H. pylori was eliminated by antibiotics, continuous exposure of human gastric cancer cells for 48 hours or longer appeared to flood the DNA-repair machinery. “DNA damage followed by potentially imprecise repair…may contribute to the genetic instability and frequent chromosomal aberrations that are a hallmark of gastric cancer,” the study authors wrote.

Dr. Richard Peek of Vanderbilt University Medical Center, whose research focuses on the role of H. pylori in gastric cancer, commented, “These findings suggest that therapies directed at reducing inflammation, without concomitant elimination of H. pylori, may not be effective in preventing DNA damage that develops in response to this pathogen.”

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