Saturday, November 5, 2011

Bacteria cause tumours by altering genetic activity

A bacterial strain is able to modify the activity of a gene, which in response causes DNA damage and correspondingly increases the risk of cancer. In a study with cell lines, cells exposed to B. fragilis were found to have two to fourfold increase of the spermine oxidase (SMO) gene. The gene codes for enzymes that are involved with oxidation processes inside cells, which can cause damage when their activity is too high. It results in inflammaton and DNA damage, both severly increasing the risk of cancer. Because bacteria reside in the colon, that is also where the increase in cancer incidence is observed. While micro-organisms, especially viruses, were already implied in various forms of cancer, it is peculiar that this form of bacteria-induced cancer works by altering the activity of a gene, instead of just causing cellular damage by producing toxins, or other pathological mechanisms.

Mice that were exposed to the gut bacterium were also found to have increased activity of the SMO gene. In addition, a mouse model that has increased risk of developing colon cancer was treated with a compound that counters the activity of SMO enzymes. This resulted in a decrease of the number of tumours, highlighting the importance of SMO in cancer development.

B. fragilis is a pathogenic bacterium that is commonly found in the gut. By unraveling the mechanism by which it can increase the risk of colon cancer, researchers have found a new target for cancer prevention therapies.  While there is already a compound that counters the effect of SMO, new therapies could be explored that kill the responsible bacterial strain. However, this would require a very specific killing mechanism, as the gut is populated by many more bacteria, that influence us in a positive way. Without them, other, pathogenic bacteria could get the chance to infect the gut and cause diseases. The native bacterial population is also needed for digestion of particular food components.

Currently, the anti-SMO drug is not suitable for use in humans. In addition to SMO, it also blocks an other enzyme, which could cause harm when patients are exposed to the drug. New drug development studies will be performed to create a drug that is selective for SMO.

Previously, scientists found that a bacterial strain called Fusobacterium can play a role in the development of colon cancer. They found that tumour tissue has much more Fusobacterium DNA than healthy tissue. While this does not prove a causal relationship, it is peculiar that the bacterium is more prevalent at spots in the colon where a tumour is growing. Therefore, it seems very likely that this bacterium also plays a role in the disease process. It was already known that Fusobacterium can be harmful, but it was not implied in cancer development before. 

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