Chen Kun-Ming, Krebs Nicolle M, Sun Yuan-Wan, Sun Dongxiao, Liao Jiangang, Reinhart Lisa, Krzeminski Jacek, Amin Shantu, Stoner Gary, Mallery Susan R, El-Bayoumy Karam
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Department of Public Health Sciences, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Carcinogenesis. 2025 Jan 20;46(1). doi: 10.1093/carcin/bgae067.
Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage induced by benzo[a]pyrene (B[a]P), 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 B[a]P 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 B[a]P 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). B[a]P-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.
我们之前通过液相色谱-串联质谱（LC-MS/MS）分析首次表明（《癌变》43:746 - 753，2022年），苯并[a]芘（B[a]P，一种口腔致癌物和烟草烟雾（TS）成分）诱导的DNA损伤水平，在吸烟者的颊细胞中显著高于非吸烟者；这些结果表明B[a]P在人类口腔鳞状细胞癌（OSCC）发展中的潜在作用。即使采用改进的靶向治疗，在晚期治疗包括OSCC在内的癌症仍然是一项重大挑战。因此，拦截/预防仍然是OSCC管理和控制的首选方法。在之前的临床前研究中，我们和其他人证明了黑树莓（BRB）对致癌物诱导的DNA损伤和OSCC具有保护作用。因此，为了转化临床前研究结果，我们在一项0期临床研究中检验了这一假设，即服用BRB可减少吸烟者颊细胞中由B[a]P诱导的DNA损伤。招募27名吸烟者后，在服用BRB含片（每天5片，共8周，每片含1克BRB粉末）之前、服用BRB的中期和末期收集基线颊细胞。最后一批样本在BRB停用后4周（洗脱期）收集。通过LC-MS/MS评估B[a]P诱导的DNA损伤（BPDE-N2-dG）。服用BRB导致DNA损伤显著减少：与基线相比，中期减少26.3%（P = 0.01506），BRB服用结束时减少36.1%（P = 0.00355），BRB停用后减少16.6%（P = 0.007586）。我们的结果表明，BRB作为一种化学预防剂，对TS引发的OSCC的发展可能具有益处。
