Dr. Marcus S. Cooke, professor and chair of the department of environmental and occupational health at the FIU Robert Stempel College of Public Health & Social Work, and an international group of researchers just published results from a study shedding light on the origin of an important biomarker.
[Photo: Dr. Marcus Cooke]
Work arising from Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS), a network of excellence operating within the European Union’s sixth Framework program, has made important progress in identifying the origin of a widely measured biomarker of oxidative stress. Oxidative stress occurs when there is an imbalance in the body’s cells between pro-oxidants (derived from environmental sources such as diet, sunlight, pollution, and smoking) and antioxidants (e.g. vitamins C and E), in favor of the former. Under oxidative stress, components of the cell are damaged with DNA, and its “building blocks” in the nucleotide pool, being particularly important targets. Damage to these components is linked to a host of major diseases, from cancer to neurodegenerative disease. Oxidative stress can be assessed noninvasively in vivo by measuring the products of this damage, such 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) in urine. Urinary 8-oxodG has been extensively studied (over 925 articles in the scientific literature, over a period of 28 years), and has formed much of the basis for linking oxidative stress and disease. It has been commonly assumed that 8-oxodG arises from DNA following its repair. In fact, the source of this damage remains unknown, severely limiting the extent of our interpretation and understanding of the role of this biomarker in disease.
In the present study, Dr. Cooke and his international team of researchers demonstrate that two major DNA repair pathways (global genome nucleotide excision repair and transcription-coupled nucleotide excision repair) do not act upon 8-oxodG. This eliminates them as contributors to urinary 8-oxodG, and calls into question the accuracy of describing urinary 8-oxodG as a biomarker of DNA oxidation. Attention is now shifting to the building blocks of DNA as potential source of this valuable biomarker.
According to Dr. Cooke, these findings are essential because “we have been measuring this product for many years, there are numerous studies, using this biomarker, demonstrating that oxidative stress is important in disease, but we’ve only been guessing from where it originates. This study narrows down considerably, those guesses.”