Inhibition of Benzoapyrene-induced DNA Adduct in Buccal Cells of Smokers by Black Raspberry Lozenges

Abstract Using LC–MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746–753, 2022) that levels of DNA damage induced by benzoapyrene (BaP), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in nonsmokers; these results suggest the potential contribution of BaP in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC, at late stages, even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies, we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings, we tested the hypothesis in a Phase 0 clinical study that BRB administration reduces DNA damage induced by BaP in the buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected 4 weeks after BRB cessation (washout period). BaP-induced DNA damage (BPDE-N2-dG) was evaluated by LC–MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (P = .01506) compared to baseline, 36.1% at the end of BRB administration (P = .00355), and 16.6% after BRB cessation (P = .007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.