We had previously shown in a human feeding study that ingestion of tomato and carrot juices decreases DNA breaks and oxidized pyrimidine bases in peripheral lymphocytes and enhances expression of glutathione S-transferase (GST) in a subpopulation of the volunteers. The aim of this study was to determine how the major carotenoids of these juices (β-carotene or lycopene) could contribute to the observed antigenotoxicity. Physiological concentrations (2 μM) of water-soluble β-carotene and lycopene were incubated for 18–24 h with lymphocytes and then treated with bleomycin or H 2 O 2 . Strand breaks, oxidized DNA bases, and persistence of damage (DNA repair) were measured by single-cell microgelelectrophoresis. GST–protein (GSTP1) was determined using an immunoassay and by measuring enzyme activity. HPLC analysis showed that β-carotene was taken up by the cells after 24 h, and this was associated with a reduction of bleomycin-induced damage (29.11 ± 1.86% tail intensity without versus 21.54 ± 2.36% with β-carotene). Lycopene was ineffective. The carotenoids did not modulate repair of bleomycin- and H 2 O 2 -induced damage and did not alter levels of oxidized pyrimidine bases nor GST expression. The results indicate that β-carotene can enter the cell and protect against strand breaks but not against oxidized DNA bases. Therefore, β-carotene accounts for only part of the protection observed in vivo with carotenoid-rich vegetable juices.