It is expected that in 2016, there will be an estimated 48,330 new cases and 9,570 deaths due to oral cancer in the US, which is about one person every hour every day. Due to the epithelial field defects associated with oral carcinogenesis, tumor recurrence and second primary tumor incidence are common. Recently conducted Phase I Clinical trials demonstrate the ability of black raspberries (BRBs) to modulate inflammatory biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. From these human trials we have established a molecular signature of BRB responsive biomarkers. However, it is essential that a preclinical animal model of BRB chemoprevention which recapitulates the fundamental features of human oral carcinogenesis be developed, so that we can evaluate potential mechanisms of action and validate molecular biomarkers of BRB efficacy. We therefore established the ability of BRB to inhibit oral lesion formation in a rat model of 4-nitroquinoline 1-oxide (4NQO) induced oral carcinogenesis and examined molecular efficacy using a clinically relevant transcriptional signature. Oral cancer was induced in F344 rats using 4NQO in drinking water for 10 weeks followed by regular drinking water for 16 weeks. Rats were administered a diet containing 5 or 10 percent lyophilized BRBs. Tongue tissues were examined for lesion multiplicity, incidence and histopathological features. Clinically derived pro-inflammatory and pro-survival molecular biomarkers were also determined by real-time PCR and ELISA. Dietary administration of 5 and 10 percent BRBs reduced combined lesion incidence and multiplicity by -39.3% and -28.6% respectively. Histopathological analyses of tongue sections further demonstrate the chemopreventive ability of dietary BRB administration in the rat model. Pro-survival and pro-inflammatory biomarkers were downregulated in BRB administered 4NQO induced rats compared to untreated 4NQO induced rats. Our study shows that dietary administration of BRB inhibits oral carcinogenesis in the rat 4NQO model. The rat 4NQO model is suitable for interrogating mechanisms of action of BRB-mediated oral cancer chemoprevention.
Citation Format: Steve Oghumu, Thomas Knobloch, Jennifer Ahn-Jarvis, Logan Weghorst, Kyle Horvath, Paul Geuy, Christopher Weghorst. Chemoprevention of rat oral carcinogenesis by black raspberry phytochemicals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5264. doi:10.1158/1538-7445.AM2017-5264