ROLE OF OXIDATIVE DNA-DAMAGE IN HYDROXYCHAVICOL-INDUCED GENOTOXICITY

Chewing betel quid has been linked to the development of oral cancer, In Taiwan, fresh Piper betle inflorescence is uniquely added to betel quid, and hydroxychavicol is the major phenolic components of P.betle inflorescence. In this study, we tested the mutagenic potential of hyd roxychavicol in Salmonella typhimurium TA97, TA98, TA100 and TA102 wit h and without Aroclor-1254 induced S9 fraction, The results showed tha t hydroxychavicol was positive in S.typhimurium TA102 without metaboli c activation, This increase in revertants was partially inhibited by c atalase and superoxide dismutase, In Chinese hamster ovary (CHO-K1) ce lls, hydroxychavicol induced chromosome aberrations in a dose-dependen t manner (10-50 mu M) and the majority were chromosome-type aberration s, Hydroxychavicol also significantly increased the frequency of micro nuclei in CHO-K1 cells up to 3-fold at a concentration of 40 mu M. In addition, hydroxychavicol dose-dependently (0.1-20 mu M) induced coppe r-dependent strand breaks in plasmid DNA, We further tested the oxidat ive DNA damage potential of hydroxychavicol by measuring 8-hydroxydeox yguanosine (8-OH-dG) formation in CHO-K1 cells following an 18-h incub ation and found that hydroxychavicol (6.25-100 mu M) induced 8-OH-dG l evels dose-dependently, The increase of 8-OH-dG formation was positive ly correlated (r = 0.79) with the hydroxychavicol-induced cytotoxicity , In conclusion, hydroxychavicol may exert its genotoxic potential thr ough oxidative DNA damage.