DNA repair as a biomarker

摘要

DNA instability is a common factor in many human diseases, either as cause or effect. It is now common, in molecular epidemio-logical studies, to measure different kinds of DNA or chromosomal damage as markers of exposure to genotoxic agents. In the case of chromosome aberrations and micronuclei, these are also considered as predictive indicators of cancer risk [1]. DNA damage can result from a variety of environmental, genetic and metabolic influences, but is usually counteracted by the highly effective DNA repair processes operating in virtually all cell types. When we measure DNA damage, for example in peripheral blood mononuclear cells (PBMC), we are looking at a dynamic steady state - an equilibrium between the input of damage and its removal by repair. Normally, these two are in balance and there is no net accumulation of damage, but the actual level of damage is influenced by the cells' capacity for repair. So, not surprisingly, DNA repair itself is seen as an important parameter, and there are a variety of ways of assessing it. These range from the genetic approach of looking for polymorphisms in DNA repair genes, to an emphasis on phenotype, whether measured as levels of expression of DNA repair genes, or activities of repair enzymes.