Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How infection can lead to cancer

12.06.2012
New MIT study offers comprehensive look at chemical and genetic changes that occur as inflammation progresses to cancer

One of the biggest risk factors for liver, colon or stomach cancer is chronic inflammation of those organs, often caused by viral or bacterial infections. A new study from MIT offers the most comprehensive look yet at how such infections provoke tissues into becoming cancerous.

The study, which is appearing in the online edition of Proceedings of the National Academy of Sciences the week of June 11, tracked a variety of genetic and chemical changes in the livers and colons of mice infected with Helicobacter hepaticus, a bacterium similar to Helicobacter pylori, which causes stomach ulcers and cancer in humans.

The findings could help researchers develop ways to predict the health consequences of chronic inflammation, and design drugs to halt such inflammation.

"If you understand the mechanism, then you can design interventions," says Peter Dedon, an MIT professor of biological engineering. "For example, what if we develop ways to block or interrupt the toxic effects of the chronic inflammation?"

Dedon is one of four senior authors of the paper, along with Steven Tannenbaum, a professor of biological engineering and chemistry; James Fox, a professor of biological engineering and director of the Department of Comparative Medicine; and Gerald Wogan, a professor of biological engineering and chemistry. Lead author is Aswin Mangerich, a former MIT postdoc now at the University of Konstanz in Germany.

Too much of a good thing

For the past 30 years, Tannenbaum has led a group of MIT researchers dedicated to studying the link between chronic inflammation and cancer. Inflammation is the body's normal reaction to any kind of infection or damage, but when it goes on for too long, tissues can be damaged.

When the body's immune system detects pathogens or cell damage, it activates an influx of cells called macrophages and neutrophils. These cells' job is to engulf bacteria, dead cells and debris: proteins, nucleic acids and other molecules released by dead or damaged cells. As part of this process, the cells produce highly reactive chemicals that help degrade the bacteria.

"In doing this, in engulfing the bacteria and dumping these reactive chemicals on them, the chemicals also diffuse out into the tissue, and that's where the problem comes in," Dedon says.

If sustained over a long period, that inflammation can eventually lead to cancer. A recent study published in the journal The Lancet found that infections account for about 16 percent of new cancer cases worldwide.

Widespread damage

In the new MIT study, the researchers analyzed mice that were infected with H. hepaticus, which causes them to develop a condition similar to inflammatory bowel disease in humans. Over the course of 20 weeks, the mice developed chronic infections of the liver and colon, with some of the mice developing colon cancer.

Throughout the 20-week period, the researchers measured about a dozen different types of damage to DNA, RNA and proteins. They also examined tissue damage and measured which genes were turned on and off as the infection progressed. One of their key findings was that the liver and colon responded differently to infection.

In the colon, but not the liver, neutrophils secreted hypochlorous acid (also found in household bleach), which significantly damages proteins, DNA and RNA by adding a chlorine atom to them. The hypochlorous acid is meant to kill bacteria, but it also leaks into surrounding tissue and damages the epithelial cells of the colon.

The researchers found that levels of one of the chlorine-damage products in DNA and RNA, chlorocytosine, correlated well with the severity of the inflammation, which could allow them to predict the risk of chronic inflammation in patients with infections of the colon, liver or stomach. Tannenbaum recently identified another chlorine-damage product in proteins: chlorotyrosine, which correlates with inflammation. While these results point to an important role for neutrophils in inflammation and cancer, "we don't know yet if we can predict the risk for cancer from these damaged molecules," Dedon says.

Another difference the researchers found between the colon and the liver was that DNA repair systems became more active in the liver but less active in the colon, even though both were experiencing DNA damage. "It's possible that we have kind of a double whammy [in the colon]. You have this bacterium that suppresses DNA repair, at the same time that you have all this DNA damage happening in the tissue as a result of the immune response to the bacterium," Dedon says.

The researchers also identified several previously unknown types of damage to DNA in mice and humans, one of which involves oxidation of guanine, a building block of DNA, to two new products, spiroiminodihydantoin and guanidinohydanotoin.

In future studies, the MIT team plans to investigate the mechanisms of cancer development in more detail, including looking at why cells experience an increase in some types of DNA damage but not others.

The research was funded by the National Cancer Institute.

Written by Anne Trafton, MIT News Office

Anne Trafton | EurekAlert!
Further information:
http://www.mit.edu

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>