Effects of quercetin on β-apo-8′-carotenal-induced DNA damage and cytochrome P1A2 expression in A549 cells

We compared the effects of beta-carotene with those of beta-apo-8'-carotenal (AC, an oxidative product of beta-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 beta-carotene or AC for I h, followed by incubation with 20 mu M 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 beta-carotene and AC at 20 mu M significantly enhanced DNA strand breaks and CYP1A2 expression induced by BaP However, beta-carotene at 2 mu M 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 beta-carotene and AC on intracellular DNA were associated with the expression of CYP, because I-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 beta-carotene in combination with BaP or by AC alone. These findings indicate that the harmful effect of beta-carotene induced by BaP may be through the formation of oxidative products such as AC. Quercetin increased the safety of high doses of beta-carotene, possibly through interaction with beta-carotene's oxidative products or through inhibition of CYP1A2 expression. (c) 2006 Elsevier Ireland Ltd. All rights reserved.