Basil extract inhibits the sulfotransferase mediated formation of DNA adducts of the procarcinogen 1′-hydroxyestragole by rat and human liver S9 homogenates and in HepG2 human hepatoma cells

The effects of a basil extract on the sulfation and concomitant DNA adduct formation of the proximate carcinogen 1′-hydroxyestragole were studied using rat and human liver S9 homogenates and the human hepatoma cell line HepG2. Basil was chosen since it contains the procarcinogen estragole that can be metabolized to 1′-hydroxyestragole by cytochrome P450 enzymes. Basil extract addition to incubations of rat and human liver S9 homogenates with 1′-hydroxyestragole, the sulfotransferase cofactor PAPS, and 2′-deoxyguanosine resulted in a dose-dependent inhibition of N2-(trans-isoestragol-3′-yl)-2′-deoxyguanosine formation. Because the inhibition resembled the inhibition by the sulfotransferase inhibitor pentachlorophenol and since the inhibition was not observed in incubations with the direct electrophile 1′-acetoxyestragole it is concluded that the inhibition occurs at the level of the sulfotransferase mediated bioactivation step. Additional experiments in HepG2 cells revealed the same protective effect of basil extract in intact cells, demonstrating that the inhibitors are able to enter the cells. The results of this study suggest that bioactivation and subsequent adverse effects of 1′-hydroxyestragole might be lower in a matrix of other basil ingredients than what would be expected on the basis of experiments using 1′-hydroxyestragole as a single compound. © 2008 Elsevier Ltd. All rights reserved. Chemicals / CAS: 1' hydroxyestragole, 51410-44-7; cytochrome P450, 9035-51-2; deoxyguanosine, 961-07-9; DNA, 9007-49-2; estragole, 140-67-0; sulfotransferase, 9023-09-0; 1'-hydroxyestragole, 51410-44-7; Anisoles; Deoxyguanosine, 961-07-9; DNA Adducts; Enzyme Inhibitors; Plant Extracts; Sulfotransferases, EC 2.8.2.-; Tetrazolium Salts; Thiazoles; thiazolyl blue, 298-93-