The role of dietary antioxidants in human health remains controversial. Fruits and vegetables in the diet are associated with lower rates of chronic disease, and this is often attributed to their content of antioxidants, and a resulting protection against oxidative stress. However, large-scale human trials with antioxidant supplements have shown, if anything, an increase in mortality. We have investigated the biological properties of beta-cryptoxanthin, a common carotenoid, in cell culture model systems, using the comet assay to measure DNA damage. At low concentrations, close to those found in plasma, beta-cryptoxanthin does not itself cause damage, but protects transformed human cells (HeLa and Caco-2) from damage induced by H(2)O(2) or by visible light in the presence of a photosensitizer. In addition, it has a striking effect on DNA repair, measured in different ways. Incubation of H(2)O(2)-treated cells with beta-cryptoxanthin led to a doubling of the rate of rejoining of strand breaks and had a similar effect on the rate of removal of oxidized purines by base excision repair. The latter effect was confirmed with an in vitro assay: cells were incubated with or without beta-cryptoxanthin before preparing an extract, which was then incubated with substrate DNA containing 8-oxo-7,8-dihydroguanine; incision was more rapid with the extract prepared from carotenoid-preincubated cells. No significant increases were seen in protein content of human 8-oxoguanine DNA glycosylase 1 or apurinic endonuclease 1. The apparent cancer-preventive effects of dietary carotenoids may depend on the enhancement of DNA repair as well as antioxidant protection against damage.