Effects of Black Raspberry on DibenzoPyrene Diol Epoxide Induced DNA Adducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity.
Cancer Prev Res (Phila). 2018 Mar ;11(3):157-164. Epub 2017 Nov 20. PMID: 29158340
We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzopyrene (DBP) to its active fjord region diol epoxide (DBPDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DBPDE does not require metabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5% added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in thegene in the mouse oral cavity. We showed that BRB inhibited DBPDE-induced DNA damage (<0.05) and mutagenesis (= 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5% BRB was significantly (<0.05) reduced from 93% to 66%. Specifically, the incidence of benign tumor was significantly (<0.001) reduced from 90% to 31% (62% to 28% in the oral cavity and 28% to 2% in the tongue), a nonsignificant reduction of malignant tumors from 52% to 45%. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens..