Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9031120 | Food and Chemical Toxicology | 2005 | 9 Pages |
Abstract
Aim of the present experiments was to study the genotoxic effects of coffee diterpenoids, namely cafestol palmitate and a mix of cafestol and kahweol (C + K) in human derived hepatoma (HepG2) cells. Furthermore, we investigated the potential protective properties of these substances towards carcinogens contained in the human diet, namely N-nitrosodimethylamine (NDMA) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). C + K and cafestol palmitate were tested over a broad dose range in micronucleus (MN) assays and no indication for genotoxic effects was seen. In combination experiments with PhIP (300 μM), pronounced inhibition (â1.7-fold) of MN formation was observed with C + K and cafestol palmitate at dose levels ⩾0.9 and 1.7 μg/ml, respectively. Enzyme measurements indicate that the protection is due to inhibition of sulfotransferase, an enzyme involved in the activation of the amine, and/or to induction of UDP-glucuronosyltransferase which detoxifies the DNA-reactive metabolites of PhIP. Furthermore, a significant increase of glutathione-S-transferase was seen, whereas the activities of cytochrome P-450 1A1 and N-acetyltransferase 1 were not significantly altered. Also in combination experiments with C + K and NDMA, strong protective effects (50% reduction of genotoxicity) were seen at low dose levels (⩾0.3 μg/ml). Since inhibition of MN was also observed when C + K were added after incubation with NDMA, it is likely that the chemoprotective effects are due to induction of DNA repair enzymes. Comparison of data on the effects of C + K on the cholesterol metabolism, which was investigated in earlier in vivo studies, with the present findings suggests that DNA-protective effects take place at exposure levels which are substantially lower than those which cause hypercholesterolemia.
Keywords
HepG2DMEM, Dulbecco’s minimal essential mediumB(a)P, benzo[a]pyrenePhIPAFB1, aflatoxin B1CDNB, 1-chloro-2,4-dinitrobenzeneCYP, cytochrome P-450EROD, ethoxyresorufin O-deethylaseGST, glutathione-S-transferaseKahweolMGMT, O6-methylguanine-DNA methyltransferaseMN, micronucleiN-nitrosodimethylamineNAT, N-acetyltransferaseNDMA, N-nitrosodimethylaminePhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridineSULT, sulfotransferaseMetabolic enzymesDMSO, dimethyl sulfoxidePBS, phosphate buffered salineAntimutagenicityMicronucleusCafestol
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Authors
B.J. Majer, E. Hofer, C. Cavin, E. Lhoste, M. Uhl, H.R. Glatt, W. Meinl, S. Knasmüller,