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.