Characterization of human isogenic epithelial cell lines as a relevant tool to study colon carcinogenesis and interactions between genes and environment.

Colorectal cancer, the third most common cancer worldwide, represents a major public health challenge. While only 5-10% of cases are linked to inherited genetic mutations, environmental factors play a crucial role. Epidemiological evidence suggests that diet alone may account for 30-70% of cases, making it a primary source of exposure to environmental contaminants in the colon. The disease develops progressively through the accumulation of genetic alterations, including loss of tumor suppressor gene function (APC and TP53) and activation of the proto-oncogene K-Ras. Understanding the complex interactions between genetic predisposition and environmental exposures requires advanced experimental models. In this study, we characterized an in vitro model using a non-malignant human colonic epithelial cell line and its isogenic derivatives carrying key mutations associated with colorectal cancer. These cell lines mimic the major stages of carcinogenesis: initiation, promotion, and progression. We conducted a comprehensive analysis of their biological properties, including proliferation, migration, clonogenic capacity, apoptosis resistance, and response to genotoxic stress. Additionally, metabolic profiling and xenobiotic response assessments were performed. Multivariate analysis revealed distinct features among the cell lines, providing a robust framework to investigate how environmental factors interact with genetic susceptibility in the development of colorectal cancer.