Viral or bacterial chronic inflammations of the colon, liver or stomach are often large risk factors for cancer. A new MIT study published the Proceedings of the National Academy of Sciences provides a detailed explanation as to how infections like these can turn healthy tissues into cancerous ones.
Peter Dedon, MIT professor of biological engineering explains: “If you understand the mechanism, then you can design interventions. For example, what if we develop ways to block or interrupt the toxic effects of the chronic inflammation?”
For three decades, Tannenbaum, one of the study’s senior authors, has been MIT team leader of investigating the association between chronic inflammation and cancer. The body normally reacts with inflammation in response to any type of infection of damage. However, if an inflammation continues for too long, it can result in tissue damage. The body’s way of tackling inflammation is to activate an influx of macrophage and neutrophil cells when the immune system detects any pathogens or cell damage. The macrophages and neutrophils surround the bacteria, dead cells and debris, which consists of proteins, nucleic acids and other molecules the dead or damaged cells release. During this process, the cells produce highly reactive chemicals that help to break down the bacteria.
Dedon explains: “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.”
If the inflammation is sustained over a long period of time it can eventually lead to cancer.
The Lancet recently published a study revealing that 16% of new cancer cases globally are caused by infections.
The researchers used mice that were infected with Helicobacter hepaticus to examine different chemical and genetic changes in the animals’ livers and colons. Helicobacter hepaticus is a similar bacterium to Helicobacter pylori, which causes them to develop a condition similar to inflammatory bowel disease, stomach ulcers and cancer in humans. The results could help in developing new predictive markers for chronic inflammation, as well as develop drugs to stop such inflammation.
Over the 20-week study period, the team continued measuring almost a dozen different types of DNA, RNA and protein damage, and observed that the mice developed chronic liver and colon infections, whilst some animals developed colon cancer. They also examined tissue damage and as the infection progressed, they identified which genes were turned on and off.
They made a key discovery by observing that the response to infection was different in the liver and the colon. They observed that whilst the neutrophils secreted hypochlorous acid in the colon, i.e. a substance that is also found in household bleach, which causes substantial damage to proteins, DNA and RNA by adding a chlorine atom, it did not do so in the liver, and even though the hypochlorous acid is designed to eliminate bacteria, it leaks into surrounding tissue, damaging the colon’s epithelial cells.
The team discovered that chlorocytosine, a level of one of the chlorine-damage products in DNA and RNA is strongly linked to the severity of the inflammation, and could be used as a risk-predicting marker of chronic inflammation in patients with infections of the stomach, liver or colon.
Tannenbaum and his team recently discovered another chlorine-damage product in proteins that is linked to inflammation, chlorotyrosine. Dedon says that although these results suggest that neutrophils play a significant role in inflammation and cancer, he continues stating: “we don’t know yet if we can predict the risk for cancer from these damaged molecules.”
The team also observed another difference between the liver and the colon, i.e. although both organs had DNA damage, the DNA repair systems became more active in the liver but less active in the colon.
Dedon states:
“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.”
The team, furthermore, discovered several types DNA damage in mice and humans that were previously unknown. One type of DNA damage involves guanine, a DNA building block to oxidate to two new products, namely guanidinohydanotoin and spiroiminodihydantoin.
The MIT team is planning to research the dynamics of cancer development in more detail in the future. They want to investigate the reasons for some type of cells having a higher level of DNA damage whilst other cells do not.
Written By Petra Rattue