Oxidative DNA damage: relation to cancer development

HE Poulsen, MD

Rigshospitalet, University Hospital, Copenhagen, Denmark

AIM: to develop and use methods for testing whether oxidative DNA modification relates to cancer development. METHODS: eliminate artifacts in methods for measuring DNA oxidation in humans and to test if artifact-free measures of oxidative DNA is influenced by antioxidant intervention or relates to known risk factors. RESULTS: Artifacts in the measurements has been identified and eliminated. Methods based on HPLC with tandem mass spectrometry have been developed for use in large-scale human investigations, i.e. epidemiological or intervention studies. A series of intervention studies with antioxidants such as vitamin C, vitamin E and &beta carotene and some combinations thereof have not shown any effects on oxidative DNA damage, whereas a diet supplemented with Brussels Spouts decreases it. Factors that increase oxidative DNA modifications are gender, smoking and occupations exposures such as bus driving. CONCLUSIONS: Much mechanistic evidence and observations in animals indicate a relation between oxidative DNA modification and cancer development. In humans the evidence is less evident. The methodology developed makes it possible to conduct large-scale studies. The basic and mechanistic evidence makes it reasonable to perform human studies to clarify the contribution from environmental and endogenous sources to oxidative DNA modification and if there, in humans, is a link between cancer and oxidative DNA modification. This can be done by twin studies and by case control studies in selected cancer forms. Such studies are under way.

KEY WORDS: oxidative DNA damage, smoking , antioxidant intervention, mass spectrometry.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Environment and Occupation.