Mechanism of DNA damage induced by arecaidine: The role of Cu(II) and alkaline conditions

Betel quid chewing is a widely prevalent habit correlated with a high incidence of oral cancer. However, the underlying mechanism of the carcinogenicity of betel quid chewing is poorly understood. In the present study, the carcinogenic mechanism of action of betel quid chewing was examined by determining DNA damage induced by arecaidine and Cu(II). It was found that arecaidine alone had no significant effect on inducing DNA damage, but it caused significant DNA double stand breaks in the presence of Cu(II) ions under alkaline conditions. Further studies showed that reactive oxygen species were generated and Cu(I) was formed in the reaction. The arecaidine anion exhibited a lower IP and a higher HOMO energy than arecaidine itself, suggesting an increased ability to donate electrons under alkaline pH conditions. These results suggest that the presence of Cu(II) and alkaline conditions are two essential factors in arecaidine-induced DNA damage, a contributing factor to oral cancer occurrence.