The Impact of Black Raspberry As a Whole Food Approach on DNA Damage-Induced by Tobacco Carcinogens in the Oral Cavity and Urine of Smokers

Introduction. We recently reported that black raspberries (BRB) powder inhibits dibenzo[def,p]chrysene (also known as dibenzo[a,l]pyrene; DBP) and its diolepoxides-induced DNA damage, mutagenesis and oral squamous cell carcinoma (OSCC) development in mice. We also showed that BRB enhanced DNA repair capacity of DNA damage-induced by DBP and altered genetic and epigenetic markers in a manner consistent with its cancer prevention activity. Polycyclic aromatic hydrocarbons (PAHs) are recognized as potential etiological agents in the development of oral cancer in smokers. In particular, benzo[a]pyrene (B[a]P) and DBP are detected in cigarette smoke and the environment; they can induce DNA damage, mutagenesis and carcinogenesis in the oral cavity of rodents. Consequently, their DNA adducts are regarded as the most direct markers of genotoxicity and can be used as biomarkers of cancer risk. Therefore, to translate our preclinical findings, we initiate a clinical study to examine the effects of BRB lozenges on DNA damage in smokers’ buccal cells. Experimental procedures. As an initial step for method development to examine the effects of BRB in humans, we conducted a study using LC-MS/MS analysis with isotope labelled internal standard to detect and quantify DNA adducts derived from B[a]P and DBP in buccal cells of cigarette smokers and non-smokers. Participants in this study include 21 smokers and 16 non-smokers. The urinary level of 8-oxodG (a marker of oxidative DNA damage) of smokers was also analyzed by LC-MS/MS. Results. Our results are the first to report that levels (mean ± S.D.) of BPDE-N2-dG were significantly higher in smokers (20.18 ± 8.40 adducts/108 dG) than in non-smokers (0.84 ± 1.02 adducts/108 dG). Likewise, levels of DBPDE-N6-dA in smokers (5.49 ± 3.41 adducts/108 dA) were significantly higher than non-smokers (2.76 ± 2.29 adducts/108 dA). Furthermore, we found that the baseline level of 8-oxodG in smokers’ urine before consumption of BRB lozenges is 18.92 ± 11.53 pmol/mL (n = 6). This level was significantly decreased by 16% (p = 0.006) during the consumption of BRB lozenges, and the level was decreased by 23% (p = 0.06) after cessation of BRB lozenges. Conclusion. Collectively, the results of this clinical study demonstrats that PAHs in tobacco smoke can contribute to the development of oral cancer in humans. Our results also suggest that BRB inhibited oxidative DNA damage in smokers’ urine. Currently, we are focusing on examining the effects of BRB on DNA damages induced by B[a]P and DBP in smokers. Supported by NIH grant #CA173465. Citation Format: Kun-Ming Chen, Yuan-Wan Sun, Nicolle M. Krebs, Lisa Reinhart, Dongxiao Sun, Elizabeth P. Bond, Jacek Krzeminski, Krishne Gowda, Shantu Amin, Susan Mallery, John P. Richie, Karam El-Bayoumy. The impact of black raspberry as a whole food approach on DNA damage-induced by tobacco carcinogens in the oral cavity and urine of smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3337.