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 hydroxychavicol in Salmonella typhimurium TA97, TA98, TA100 and TA102 with and without Aroclor-1254 induced S9 fraction. The results showed that hydroxychavicol was positive in S.typhimurium TA102 without metabolic activation. This increase in revertants was partially inhibited by catalase and superoxide dismutase. In Chinese hamster ovary (CHO-K1) cells, hydroxychavicol induced chromosome aberrations in a dose-dependent manner (10-50 microM) and the majority were chromosome-type aberrations. Hydroxychavicol also significantly increased the frequency of micronuclei in CHO-K1 cells up to 3-fold at a concentration of 40 microM. In addition, hydroxychavicol dose-dependently (0.1-20 microM) induced copper-dependent strand breaks in plasmid DNA. We further tested the oxidative DNA damage potential of hydroxychavicol by measuring 8-hydroxydeoxyguanosine (8-OH-dG) formation in CHO-K1 cells following an 18-h incubation and found that hydroxychavicol (6.25-100 microM) induced 8-OH-dG levels dose-dependently. The increase of 8-OH-dG formation was positively correlated (r = 0.79) with the hydroxychavicol-induced cytotoxicity. In conclusion, hydroxychavicol may exert its genotoxic potential through oxidative DNA damage.