Development of Primary Colon and Duodenal Tumor Cultures from the Apc-mutant Pirc Rat for Screening Preventive Agents

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with genetic, epigenetic, and immune-dependent mechanisms contributing to disease pathogenesis. Preventive strategies are especially important for individuals with hereditary syndromes such as familial adenomatous polyposis (FAP), in which Adenomatous Polyposis Coli (APC) mutations drive early tumor formation. The polyposis in rat colon (Pirc) model, harboring an Apc mutation, faithfully recapitulates the development of adenomatous polyps, a precursor stage of CRC, in both the colon and duodenum. Here, we report the generation and characterization of primary cell cultures derived from 30 colonic and duodenal adenomas (benign tumors) from Pirc rats. These Pirc colon adenoma and duodenal adenoma cultures demonstrated consistent morphology, epithelial marker expression (E-cadherin and pan-cytokeratin), and robust 3D spheroid formation. Growth kinetics revealed a doubling time of 50 ± 4 hours. Notably, histone deacetylase and bromodomain inhibitors reduced cell viability and colony formation significantly, highlighting the synergistic potential in targeting deregulated epigenetic signatures as early-stage prevention strategies in FAP. These primary cultures, maintained between passages 5 and 10 to preserve phenotypic integrity, offer a valuable ex vivo model for early-stage CRC research and the screening of preventive agents. By bridging genetic susceptibility and translational prevention, this platform provides a novel and reproducible tool for advancing cancer interception.