A lung cancer mouse model system based on an inbred C3H strain: Ultrasound imaging, pathological analysis, and proteomic biomarker identification

Background and Aim: Lung cancer remains a leading cause of global mortality, necessitating robust animal models for
research into its mechanisms and therapeutic options. This study aimed to develop and validate a novel lung cancer
mouse model using the inbred C3H strain through intraperitoneal (I.P) injection of benzo(a)pyrene, offering insights into hematology, pathology, imaging, and proteomic biomarkers. Materials and Methods: Twelve male inbred C3H mice were assigned to non-treated and treatment groups, with the latter receiving 100 mg/kg body weight of benzo(a)pyrene intraperitoneally. Tumor development was monitored for 15 days using hematological analysis, ultrasound imaging (Vevo F2), histopathological assessment, and proteomic profiling through liquid chromatography-high-resolution mass spectrometry. Results: Hematological analysis indicated a decrease in white blood cells, lymphopenia, and neutropenia, while red
blood cells, hemoglobin, and platelets remained within normal ranges. Ultrasound imaging revealed tumor formation as hypoechoic areas with irregular patterns on the lung surface. The histological analysis highlighted lymphocyte infiltration, alveolar wall thickening, fibroelastosis, and dysplastic changes in the bronchial epithelium. Proteomic profiling identified specific biomarkers associated with lung cancer, including A disintegrin and metalloproteinase with thrombospondin motifs 12, abnormal spindle, adducin-3, adhesion G protein-coupled receptor, Agrin, apoptotic chromatin condensation inducer 1, rapidly accelerated fibrosarcoma isoforms B oncogene, breast cancer gene 2, hypoxia-induced gene-1, leucine-rich repeat-containing 2, leucine-rich repeat kinase 2, leucine-rich repeat-containing protein 2 isoform X2, membrane-spanning 4-domains, subfamily A, proto-oncogene tyrosine-protein kinase Src, rat sarcoma virus-related protein 14, squamous cell carcinoma antigen, and transcription intermediary factor 1-alpha. Conclusion: The I.P administration of benzo(a)pyrene in C3H mice effectively induced lung cancer, demonstrating significant pathological and biomarker changes. This model provides a valuable platform for investigating lung cancer mechanisms, evaluating new therapeutic approaches, and potentially shortening the timeframe required to establish reliable animal models for preclinical studies.