β-Carotene Exacerbates DNA Oxidative Damage and Modifies p53-Related Pathways of Cell Proliferation and Apoptosis in Cultured Cells Exposed to Tobacco Smoke Condensate

D ow nloaded from Human intervention trials have shown that supplemental β-carotene increases cancer risk in smokers, but the mechanism(s) underlying this effect is still unknown. The aim of this study was to evaluate the effects of an association of cigarette smoke condensate (TAR) and β-carotene on DNA oxidative damage and molecular pathways involved in cell cycle progression and apoptosis in cultured cells. In RAT-1 fibroblasts, TAR caused increased levels of 8-OHdG and this effect was enhanced by the concomitant presence of β-carotene (0.5-4.0 µM) in a dose- and time-dependent manner. In contrast, β-carotene alone did not significantly modify it. Fibroblasts treated with TAR alone decreased their cell growth with respect to control cells through an arrest of cell cycle progression in the G0/G1 phase and an induction of apoptosis. These effects were accompanied by an increased expression of p53, p21 and Bax and by a decreased expression of cyclin D1. In contrast, fibroblasts treate