Probe to detect faulty DNA

C&I Issue 3, 2015

What if we could spot the first tiny steps on the way to full-blown cancer?  This is the promise held out by a new study showing that tweaks in genes, caused by activities like smoking, can be flagged almost as they happen.

In most cases, cancer is caused by a minor change in a person’s DNA. This change occurs on exposure to alkylating agents – especially nitrosamines, present in the environment, in food and in tobacco smoke – which react with the DNA bases to create adducts or ‘tags’ that cause havoc when genes are read or ‘translated’, sometimes resulting in faulty proteins.

At ETH in Zurich, Switzerland, toxicologist Shana Sturla and colleagues have developed a probe that recognises DNA adducts. The probe is a synthetic DNA building block that binds to a damaged form of the DNA base guanine at a specific point (JACS., doi: 10.1021/ja5100542). 

In future, Sturla envisages the development of perhaps half a dozen probes to spot the major DNA modifications involved in cancers.  ‘Large-scale population studies could be done that really link chemical exposures with risk of developing cancer, whereas now we have only limited studies regarding DNA adducts. This could allow us have a deep understanding of how this type of DNA damage really impacts on our risk of developing cancer,’ she explains.A second opportunity is to harness these biomarkers for ‘monitoring exposures and helping people make decisions about their diet or lifestyle,’ says Sturla. ‘People think of cancer often as unpredictable, partly because there is a lack of feedback mechanisms, but this could allow you to detect pre-cancerous events.’

It would also be possible to quantify the amount of damage and score a person’s progress in reducing adducts as a marker of cancer risk. This is because the marker could be directly measured by chemical analysis techniques.

‘This is a potentially exciting development,’ comments Stephen Hecht at the University of Minnesota, US, who describes the work as ‘superb’.

‘This new approach, when fully developed, could greatly facilitate the detection of specific types of DNA damage, which would be important for determining susceptibility to cancer, and for early detection of cancer,’ he says.

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