Abstract We compared the effects of β-carotene with those of β-apo-8′-carotenal (AC, an oxidative product of β-carotene) on DNA damage and the expression of cytochrome P450 (CYP)1A2 in A549 cells exposed or not to benzo[ a]pyrene (BaP), a cigarette-associated carcinogen. Furthermore, we investigated whether quercetin, a flavonoid, modulates these effects. A549 cells were first preincubated with various concentrations of β-carotene or AC for 1 h, followed by incubation with 20 μM BaP for 24 h. Next, DNA strand breaks, measured by use of the comet assay, and the expression of CYP1A2, measured by use of western blotting, were assessed. Both β-carotene and AC at 20 μM significantly enhanced DNA strand breaks and CYP1A2 expression induced by BaP. However, β-carotene at 2 μM significantly suppressed BaP-induced DNA strand breaks. AC alone induced DNA strand breaks, lipid peroxidation, and the expression of CYP1A2 in A549 cells. The harmful effects of β-carotene and AC on intracellular DNA were associated with the expression of CYP, because 1-aminobenzotriazole, a CYP inhibitor, partly suppressed these effects. Quercetin significantly inhibited the DNA strand breaks and the increase in CYP1A2 protein induced by AC or β-carotene in combination with BaP or by AC alone. These findings indicate that the harmful effect of β-carotene induced by BaP may be through the formation of oxidative products such as AC. Quercetin increased the safety of high doses of β-carotene, possibly through interaction with β-carotene's oxidative products or through inhibition of CYP1A2 expression.