Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


How infection can lead to cancer

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:

More articles from Health and Medicine:

nachricht Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital

nachricht Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University

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: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Prototype device for measuring graphene-based electromagnetic radiation created

28.10.2016 | Power and Electrical Engineering

Gamma ray camera offers new view on ultra-high energy electrons in plasma

28.10.2016 | Physics and Astronomy

When fat cells change their colour

28.10.2016 | Life Sciences

More VideoLinks >>>