Effects of quercetin on beta-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 1h, followed by incubation with 20 microM BaP for 24h. 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 microM significantly enhanced DNA strand breaks and CYP1A2 expression induced by BaP. However, beta-carotene at 2 microM 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 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 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.
Yeh
Shu-Lan
SL
Institute of Nutritional Science, Chung Shan Medical University, No. 110 Section 1 Chien-Kuo N. Road, Taichung, Taiwan, ROC. suzyyeh@csmu.edu.tw <suzyyeh@csmu.edu.tw>
Wu
Shu-Hsuan
SH
D000975:Antioxidants / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D015153:Blotting, Western; D002338:Carotenoids / Q000378:metabolism* / Q000633:toxicity; D045744:Cell Line, Tumor; D020552:Comet Assay; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D053960:DNA Breaks; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D011794:Quercetin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D019207:beta Carotene / Q000378:metabolism* / Q000633:toxicity
D000975:Antioxidants; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D014230:Triazoles; C110652:beta-apo-8'-carotenal; D019207:beta Carotene; C033020:1-aminobenzotriazole; D001564:Benzo(a)pyrene; D002338:Carotenoids; D011794:Quercetin; D019388:Cytochrome P-450 CYP1A2