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. The compound itself was devoid of mutagenic activity at all concentrations tested. In the micronucleus (MN) assay with human-derived HepG2 cells, a different pattern of activity was seen. CR itself caused significant induction of MN at dose levels > or =15 microg/ml; in combination experiments with B(a)P and
PhIP, U-shaped dose-response curves were obtained and protection was found only in a narrow dose range (5 - 10 microg/ml). Our findings indicate that the molecular mechanisms that account for the
antimutagenic effects of CR in bacterial cells are different from those responsible for the effects in HepG2 cells. Earlier reports indicate that the
antimutagenic effects of CR towards B(a)P and heterocyclic
amines in bacterial indicators is due to inhibition of the activity of CYP1A. In contrast to this, we found a significant induction of
CYP1A1 activity in HepG2 cells by CR. It can also be excluded that induction of GST, which is involved in the detoxification of
polycyclic aromatic hydrocarbons accounts for the protective effects of CR against B(a)P since this
enzyme was not significantly induced in the HepG2 cells. In the case of
PhIP, induction of UDGPT and/or inhibition of
sulfotransferase seen in human derived HepG2 cells after exposure to CR might play a role in the
antimutagenic effects. In conclusion, our findings show that data from antimutagenicity studies with bacterial indicators cannot be extrapolated to HepG2 cells, and that CR causes genotoxic effects at higher dose levels in the latter cells. The implications of these observations for human
chemoprevention strategies are discussed.