Nitric Oxide Shown To Cause Colon Cancer

Scientists have long established a link between inflammation, cancer, and the compound nitric oxide, which may be produced when the immune system responds to bacterial infections, including those of the colon. However, the precise nature of the relationship was unknown--until now.

Researchers from the Massachusetts Institute of Technology's (MIT; Cambridge, MA, USA) division of comparative medicine and department of biological engineering recently discovered that nitric oxide produced by inflammatory cells during bacterial infection can cause colon cells to become cancerous. This finding suggests that suppressing the compound may help prevent or treat colon cancer, the third most common form of cancer in the United States.

The researchers, led by Dr. James Fox, director of the division of comparative medicine, reported their findings in the January 19, 2008, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS).

Many years ago, it was discovered that gastrointestinal infection by Helicobacter pylori is frequently associated with cancer in humans; a related bacteria called H. hepaticus has similar effects in mice. Nitric oxide is produced during the inflammatory response to such bacterial infection, but it has been unclear whether it was damaging cells or protecting them. By studying the mice, the MIT team revealed that nitric oxide produced by different types of cells has different effects. "Nitric oxide delivered by inflammatory cells, in particular, is important in causing changes in intestinal epithelial cells, setting the stage for cancer development,” said Dr. Susan Erdman, lead research scientist in the division of comparative medicine and lead author of the PNAS article.

In mice infected with H. hepaticus, the researchers found that blocking an enzyme required to generate nitric oxide reduced colon cancer rates. More research is needed to study the exact effects of nitric oxide and develop potential clinical therapies for colon cancer, according to Dr. Erdman. "Therapies will need to be targeted to inhibit the damaging effects of nitric oxide while preserving as many of the protective elements of nitric oxide as possible,” she said.

"This study is a wonderful example of the value and final product that results from an interdisciplinary team effort,” concluded Dr. Fox.

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