Antioxidants, DNA damage and gene expression

Reactive oxygen species (ROS) are generated from incomplete reduction in the respiratory chain. On one hand they pose a serious threat of deleterious effects on important macromolecules, among which DNA is considered most important since it carries the genetic information and changes will be carried on to future generations, or will fundamentally change the behaviour of the cells. On the other hand, it is becoming evident that there are important changes in the cells in response to redox changes. This review summarises the genes, the intracellular signalling elements and molecules that presently are known to be regulated by oxidative stress. It is now clear that both oxidants and antioxidants can regulate a multitude of different cellular functions, signal transduction pathways and gene expression. However, the quantitative importance is unknown and as of yet there are no examples of regulation exclusively by oxidative stress. Also the response to oxidative stress is variable, can be up-regulation as well as down-regulation, and different responses to dose or magnitude of the oxidative stress can be demonstrated. The effect from supplementation with an antioxidant is difficult to predict, and ultimately must be assessed in clinical trials.