Electrical conductivity spectra of hepatic tumors reflect hepatocellular carcinoma progression in mice

Abstract

Background: Electrical impedance spectroscopy is a technique which evaluates differences in dielectric properties of tissues for cancer identification. Methods: Murine hepatic cancer model was developed by intraperitoneal administration of N-nitrosodiethylamine to male BALB/c mice. Tumors obtained were evaluated for their conductivity in frequency range of (4 Hz–5 MHz). All tumors were subjected to histopathological grading and parameters such as free spacing, necrosis, and cell density were estimated on histological slides. The status of gap junctions and gap junction intercellular communication (GJIC) were studied using enzyme-linked immunosorbent assay, immunohistochemistry, dye transfer assay, and electron microscopy. Results: Histopathological investigation revealed the presence of moderately to poorly-differentiated hepatocellular carcinoma (HCC) in mice. All types of tumors showed higher electrical conductivity than normal liver tissue in frequency range (4 Hz–1 kHz). However, in frequency range (10 kHz–5 MHz) only poorly-differentiated tumors showed higher conductivity compared to normal tissue. The most prominent findings in moderately-differentiated and poorly-differentiated HCC were increased visible free spaces and necrosis respectively. The status of cell gap junctions were significantly deteriorated in tumors and a corresponding significant reduction in GJIC was also observed. These biological indicators were correlated with electrical conductivity of hepatic tumors. Conclusion: Variations in electrical conductivity spectra of hepatic tumors reflect progression of HCC. General significance: Future studies can be planned to perform hierarchical clustering of dielectric parameters with more number of tumor samples to establish dielectric spectroscopy-based classification or staging of hepatic tumors.