Oxidative stress and cancer: have we moved forward?

'Reactive species' (RS) of various types are formed in vivo and many are powerful oxidizing agents, capable of damaging DNA and other biomolecules. Increased formation of RS can promote the development of malignancy, and the 'normal' rates of RS generation may account for the increased risk of cancer development in the aged. Indeed, knockout of various antioxidant defence enzymes raises oxidative damage levels and promotes age-related cancer development in animals. In explaining this, most attention has been paid to direct oxidative damage to DNA by certain RS, such as hydroxyl radical (OH*). However, increased levels of DNA base oxidation products such as 8OHdg (8-hydroxy-2'-deoxyguanosine) do not always lead to malignancy, although malignant tumours often show increased levels of DNA base oxidation. Hence additional actions of RS must be important, possibly their effects on p53, cell proliferation, invasiveness and metastasis. Chronic inflammation predisposes to malignancy, but the role of RS in this is likely to be complex because RS can sometimes act as anti-inflammatory agents.