Title
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
Author
Jeurissen, S.M.F.
Punt, A.
Delatour, T.
Rietjens, I.M.C.M.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
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, 298-93-1
Subject
Alkenylbenzenes
DNA adducts
Estragole
Ocimum basilicum
Sulfotransferases
1' hydroxyestragole
Animals
Anisoles
Biotransformation
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Survival
Chromatography, High Pressure Liquid
Deoxyguanosine
DNA Adducts
DNA Repair
Enzyme Inhibitors
Humans
Liver
Liver Neoplasms
Ocimum basilicum
Plant Extracts
Rats
Risk Assessment
Spectrometry, Mass, Electrospray Ionization
Subcellular Fractions
Sulfotransferases
Tetrazolium Salts
Thiazoles
Ocimum
Ocimum basilicum
Rattus
To reference this document use:
http://resolver.tudelft.nl/uuid:3e63569c-6aa9-4b84-828c-2721976120e5
DOI
https://doi.org/10.1016/j.fct.2008.03.010
TNO identifier
240821
ISSN
0278-6915
Source
Food and Chemical Toxicology, 46 (6), 2296-2302
Document type
article