DNA molecules

Scientists track the influence of a cancer inhibitor on a single DNA molecule

Researchers in Delft University of Technology’s Kavli Institute of Nanoscience in The Netherlands have cast new light on the workings of the important cancer inhibitor topotecan. Little had been known about the underlying molecular mechanism, but the Delft scientists can now view the effects of the medicine live at the levelin of a single DNA molecule.

The research is being published this week in the journal Nature. The lead author of the article, Daniel Koster, will receive his PhD at TU Delft on Monday June 25, partly on the results described in the article.

The medicine investigated, topotecan, interacts with an important protein (TopoIB), causing a (cancer) cell to malfunction. The TopoIB protein is responsible for the removal of loops from DNA, which arise amongst other things during cell division. The TopoIB protein binds to the DNA molecule, clamps around it and cuts one of the two DNA strands, after which it allows it to unwind and finally joins the broken ends together. PhD candidate Daniel Koster, Master’s student Elisa Bot and researcher Nynke Dekker of the Molecular Biophysics group of the Kavli Institute of Nanoscience Delft have managed to unravel this mechanism in an extremely direct manner. In the laboratory they fixed a single DNA molecule between a glass plate and a magnetic sphere. With the help of two magnets they could both pull and twist the DNA molecule. When they added TopoIB to a twisted piece of DNA, they saw that the loops were slowly removed.

What is exceptional is that the action of one TopoIB enzyme on one DNA molecule could be observed live. In collaboration with St. Jude Children’s Research Hospital Memphis (USA) the mechanism could also be observed in living yeast cells.

Risk of Cancer

Doctors: Swedish Snus Cut Risk of Cancer

People who use Swedish moist snuff (snus) run twice the risk of developing cancer of the pancreas. This is the main result of a follow-up study conducted by Karolinska Institutet researchers amongst almost 300,000 male construction workers. The study is published today online in the prestigious medical journal The Lancet.

Tobacco smoking is a known risk factor for pancreatic cancer, which is an unusually malignant form of the disease. Since it is common for people who take snus – a tobacco product designed for insertion between the gum and upper lip – to also smoke cigarettes, the challenge facing epidemiological research into snus and cancer has been to isolate the effects of the different kinds of tobacco. What makes this new study unique is that it has been possible to study the correlation between snus and cancer risk in a large enough group of men who have never smoked. The subjects attended health check ups between 1978 and 1992, during which they were asked to report on their smoking and ’snusing’ habits. The researchers have also studied rates of oral and lung cancer amongst the men, but found no correlation to snus. "We’re actually not that surprised," says project leader Professor Olof Nyrén of the Department of Medical Epidemiology and Biostatistics. "Pancreatic cancer has been under discussion in several earlier epidemiological studies on humans, both regarding Scandinavian snus and American smoke-free tobacco. On the other hand, previous studies of oral and lung cancer in relation to Scandinavian snus have been negative." The main contribution of the new study is its conclusion that Swedish moist snus can be carcinogenic. However, the study also shows that the risks for users are small, and, as far as can be judged, much smaller than the risks associated with smoking.

"If 10,000 non-smoking snus users are monitored for ten years, according to our data, eight or nine of them will develop pancreatic cancer, as opposed to four amongst those who use neither product. But 9,991 won’t, so the odds aren’t that bad," he says. The debate on whether the net effect of snus is positive or negative has been raging for many years. Some scientists and health carers have advocated the use of snus, as it is likely to lead to that people will smoke less. However, Professor Nyrén argues that it is important to have all the facts on the table before any advice can be given about snus as a way to cut down on smoking. "We don’t only need reliable and accurate measures of the risks of both smoking and taking snus, we also need know the effects of other, alternative methods to cut smoking. We also have to be certain that an increase in snus marketing will not cause addictions in young people who otherwise wouldn’t have started to smoke," he says.

Face to face with chronic disease: Cancer

WHO estimates that 7.6 million people died of cancer in 2005 - representing 13% of deaths worldwide. Between 2005 and 2015, 84 million more people could die if urgent action is not taken. Cancer is not simply or even primarily a problem of rich countries. More than 70% of all cancer deaths occur in low and middle income countries.

Noemia Vicente Ribeiro from Brazil and Miriame Nnamusoke from Uganda are both battling cancer. Their personal stories show the tragic reality of cancer in poor countries and its strong impact on people and their families.

These two stories are the latest in the series "Face to face with chronic disease" focusing on people living with heart disease, stroke, cancer and other chronic diseases. ......go to WHO

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