Coffee diterpenes prevent the genotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-nitrosodimethylamine in a human derived liver cell line (HepG2).

Authors:
M Uhl
M Uhl
University Hospital Freiburg
Germany

Food Chem Toxicol 2005 Mar;43(3):433-41

Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.

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 microM), pronounced inhibition (approximately 1.7-fold) of MN formation was observed with C+K and cafestol palmitate at dose levels > or = 0.9 and 1.7 microg/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 (> or = 0.3 microg/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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2004.11.009DOI Listing
March 2005
1 Read

Publication Analysis

Top Keywords

cafestol palmitate
12
genotoxic effects
12
levels microg/ml
8
human derived
8
observed c+k
8
c+k cafestol
8
combination experiments
8
2-amino-1-methyl-6-phenylimidazo[45-b]pyridine phip
8
dose levels
8
effects
7
c+k
6
phip 300
4
genotoxicity low
4
low dose
4
experiments phip
4
effects combination
4
metabolites phip
4
300 microm
4
reduction genotoxicity
4
inhibition 17-fold
4

Altmetric Statistics

Similar Publications

Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N-acetyltransferase and glutathione S-transferase activities.

Environ Mol Mutagen 2004 ;44(4):265-76

Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas, USA.

Coffee drinking has been associated with reduced incidence of colorectal cancer, possibly via chemoprotection/modification of the metabolism of dietary heterocyclic amine carcinogens such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C have been shown to reduce colonic PhIP-DNA adducts by > 50%. We have used the male F344 rat to investigate the effects of dietary K/C (0. Read More

View Article
December 2004

Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and benzo(a)pyrene (B(a)P) in bacterial and human hepatoma (HepG2) cells.

Arch Toxicol 2003 Aug 11;77(8):477-84. Epub 2003 Jul 11.

Institute of Cancer Research, Borschkegasse 8A, 1090 Vienna, Austria.

The aim of the present study was to investigate the antimutagenic effects of chrysin (CR), a flavonoid compound contained in many fruits, vegetables and honey. Earlier investigations with bacterial indicators showed that CR is one of the most potent antimutagens among the flavonoids. In the present study, we tested the compound in the Salmonella strains TA98 and TA100 in combination with benzo(a)pyrene (B(a)P) and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and found pronounced protective activity over a concentration range between 10 and 100 microg/ml. Read More

View Article
August 2003

The effects of coffee on enzymes involved in metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rats.

Chem Biol Interact 2003 Jun;145(3):251-65

Division of Chemistry, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA.

The effects of coffee on the metabolism and genotoxicity of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were investigated. Coffee diminished the bacterial mutagenicity of PhIP in the Ames reversion assay through inhibition of cytochrome P450 1A2 (CYP1A2), a key enzyme involved in the metabolic activation of PhIP. When given as part of the diet (0, 1 or 5% w/w) to male Fischer-344 rats for 2 weeks, coffee affected the expression of hepatic enzymes involved in PhIP metabolism. Read More

View Article
June 2003

Genotoxic effects of dietary and lifestyle related carcinogens in human derived hepatoma (HepG2, Hep3B) cells.

Mutat Res 2004 Jul;551(1-2):153-66

Institute of Cancer Research, University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.

Aim of the study was to investigate the usefulness of two human derived hepatoma cell lines (HepG2 and Hep3B) for the detection of dietary and lifestyle related DNA-reactive carcinogens. Comparisons of the sensitivity of HepG2 cells of different origin towards benzo[a]pyrene (B(a)P) showed that strong differences exist in the induction of micronuclei (MN). The most sensitive was used for all further experiments, in which we investigated the effects of aflatoxin B(1) (AFB(1)), B(a)P, As(2)O(3), CdCl(2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), ethanol, acetaldehyde and caffeic acid in micronucleus (MN) tests. Read More

View Article
July 2004