Free radical honour for Leicester biochemist

Posted by mjs76 at Sep 28, 2010 10:00 AM |
Dr Marcus Cooke’s work on DNA damage acknowledged with prestigious award.

The Society for Free Radical Research (Europe) might sound like some sort of anarcho-libertarian political pressure group. But anyone with a working knowledge of chemistry should recall that a ‘free radical’ is actually an atom or ion which has a lone electron in its outer shell – or a molecule containing one of these – and that this is not a stable state, which makes such objects especially reactive.

Free radicals are involved in many intra-cellular reactions and hence are enormously useful in the study of molecular biology. Which brings us to Dr Marcus Cooke from our Department of Cancer Studies and Molecular Medicine, to whom the Society for Free Radical Research (Europe) has awarded the sixth Catherine Pasquier Award.

Dr Cooke’s principal area of research is oxidative stress; that is, damage to DNA caused by an excess of oxygen radicals or ‘reactive oxygen species’. Oxidation is a natural process involved in cell signalling and integral to the ageing process, but an excess of reactive oxygen species in a cell is known to be a factor in conditions such as cancer, arthritis and Alzheimer’s Disease.

Hence the widespread interest in the possible medical benefits of anti-oxidants – naturally occurring chemicals which can retard or alleviate oxidation. Healthy cells produce their own antioxidants which can keep oxidation in check but any imbalance in the oxidant-antioxidant levels can lead to DNA damage which has knock-on effects for cancer and other medical conditions.

Last year, Dr Cooke summed up the nature of his work to the ScienceWatch website in an interview (PDF) about a highly cited paper published in the Journal of the Federation of American Societies for Experimental Biology:

In layman's terms, this review summarises the effects of damage to DNA, the cell's blueprint, and how this damage might be involved in diseases, such as cancer. It describes how highly reactive chemicals known as free radicals, which can be generated by radiation, sunlight, and smoking, for example, are constantly damaging DNA. Antioxidants help to prevent this damage, and the DNA can also be repaired. However, if the antioxidants and repair processes are overwhelmed, levels of damage increase, and this leads to an increased risk of disease.”

The transitory nature of free radicals, being highly reactive, makes them difficult to measure directly which is why researchers use biomarkers – often pieces of damaged DNA known as ‘lesions’ – as indirect indices of oxidation. Much of Dr Cooke’s research has been into a DNA lesion called 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG for short) which is the most commonly studied oxidation biomarker, not least because it can be studied in an easily collected material – urine.

Some of Dr Cooke’s most recent papers have examined the advantages and disadvantages of urinanalysis of 8-oxdG as a means of measuring oxidative stress. One problem is that there are at least 20 different ways of measuring 8-oxodG in urine, ranging from mass spectrometry to electro-chemical techniques. Although all are effective at differentiating healthy patients from ill ones, the finer details of precisely how much 8-oxodG is present – hence the actual state of the patient’s health – varies between techniques.

An effort to resolve this comes from ESCULA, the European Standards Committee of Urinary (DNA) Lesion Analysis. Dr Cooke is leading the ESCULA project along with colleagues from Poland and Denmark, working towards an agreed reference range for urinary 8-oxodG as a biomarker for oxidative stress.

Dr Cooke was presented with the Catherine Pasquier Award at the annual meeting of SFRR (Europe) in Oslo earlier this month where he delivered the Catherine Pasquier Lecture and was elected to the Society Committee. The meeting was a joint event with the European Environmental Mutagen Society who awarded Dr Cooke their Young Scientist award in 2003.

The Catherine Pasquier Award and Lecture are named after Professor Catherine Pasquier, a leading French molecular biologist who was President of SFRR (Europe) prior to her death in 2002.