Cancer researchers investigate ‘smoking gun’ trail

The study into the ‘smoking gun’ trail of devastation caused to the body by substances known as ‘free radicals’ will also impact on our understanding of heart disease, neurodegenerative disease and arthritis.

Dr Marcus Cooke, Senior lecturer in the Radiation and Oxidative Stress Section at the University of Leicester, said: “Most of us have heard of free radicals, and the benefits of antioxidants which mop them up – even if it is just from cosmetics commercials“.

“However, premature aging is just the tip of the iceberg for their detrimental effects. Free radicals have been implicated in many diseases. They are arguably the most prevalent cancer causing chemicals known.

“Free radicals are highly reactive, and can cause widespread damage to cells, and in particular DNA – the cell's blueprint. Whilst it is very difficult to measure free radicals themselves, we can measure this damage as a 'smoking gun' signature of free radical activity.

“Being able to accurately and sensitively measure this damage will allow us to:

get a better understanding of the role of this damage in disease
develop assays to determine disease risk, by measuring cell damage
design strategies to prevent, or encourage repair, of this damage, and hence prevent disease

“This research is particularly important because it provides validated, non-invasive methods for assessing oxidative stress in humans. Being non-invasive this is ideal for looking in young and old patients.

“It will allow us to develop reference ranges to identify what levels of damage in urine are normal, or abnormal, for clinical application and to develop disease risk/prognostic tests.”

Dr. Cooke has been made PI of a project (Euros 45k) to undertake the Europe-wide validation of a urinary biomarker of oxidative stress.

This is one of two studies where Leicester is playing a lead role. Dr. Mark D. Evans is the Principal Investigator in a Euros 60k study to better understand the sources of biomarkers of oxidative stress in urine.

Both projects are spin-offs from a larger Euros 11 million EU Network of Excellence grant (Environment, Cancer, Nutrition and Individual Susceptibility, ECNIS, www.ecnis.org) of which Professor Peter Farmer, of the Department of Cancer Studies and Molecular Medicine, is the project lead at Leicester. (see link at end of release)

Dr Evans said: “These are projects addressing fundamental questions that have been, for the most part, overlooked. Being awarded these two complimentary projects, back-to-back gives us the unique opportunity to address questions that we, and others in the scientific community, have wanted to examine for many years. Likewise, this project incorporates worldwide collaborations between Leicester, Collegium Medicum in Bydgoszcz, Poland; DKFZ (the German Cancer Institute), Heidelberg, Germany; Institute of Cancer Research Sutton, U.K; Medical Institute of Bioregulation, Fukuoka, Japan; and Department of Toxicogenetics, University of Leiden, The Netherlands.

Dr Cooke said: “This is a further reflection of the international status of our group within the free radical and biomonitoring community. Through these projects, we are working closely with many of the top research institutes worldwide.”

Dr Cooke said Leicester would act as the hub of a worldwide network of more than 17 laboratories comparing methods of measuring damage to DNA, in urine: “Once we have agreement between methods, we can apply these methods to the study of DNA damage in disease.

The funding has allowed the formation of the European Standards Committee for Urinary (DNA) Lesion Analysis (ESCULA; http://escula.org), which involves researchers from around the world, including industrial collaborators.