Sequential analysis of diethylnitrosamine-induced hepatocarcinogenesis in rats

Abstract

Abstract. In the present study, we examined the sequential changes of diethylnitrosamine (DEN)-induced hepatocarcinogenesis in Wistar rats. After 14 weeks of DEN treatment, hyperplastic nodules developed as a consequence of the appearance of renewed hepatocytes, degenerated hepatocytes, oval cells and fibrotic changes. Total bilirubin and alanine aminotransferase levels were significantly higher in the DEN group compared to the control group throughout the experimental period. Our data may prove beneficial to future analyses of chemopreventive compounds during various stages of hepatocarcinogenesis in rats.

Activation of oxidative stress and inflammatory factors could account for histopathological progression of aflatoxin-B1 induced hepatocarcinogenesis in rat

“…The increased liver/body mass ratio is considered as a primary criterion to determine HCC development [31]. During pilot experiments, it was observed that two doses of 1 mg/kg b.w.…”

“…Histopathology is widely used to diagnose liver carcinoma in the patients and has also been employed to ascertain progression of DEN, a genotoxic agent, induced HCC in the animal models [31]. AFB1 is a common genotoxic agent which is considered accountable for prevalence of HCC in the human population; however, information is limited on histopathology of HCC induced by this agent, except an earlier report suggesting formation of liver foci as neoplastic lesions during AFB1 carcinogenesis in rat model [27].…”

“…1b). It has been described that highly pressed trabeculae with inconspicuous sinusoids due to compact cell mass give tumor appearance [37] and more often defined as FAH areas in the liver Sections (31,36). We observed similar areas in the liver sections after 10 weeks of AFB1 treatment showing compact cell mass with the infiltration of pro-inflammatory lymphocytes around (Fig.…”

“…We have made an attempt to study progressive changes in the liver histology after AFB1 intoxication to the rats and observed that at 4th week post-treatment stage, liver shows derangement in normal trabecular array of hepatocytes with a number of cells undergoing necrosis, and thus, could be considered to represent beginning of HCC development. Group of cells making mixed cell foci (MCF: with differential cytoplasmic staining) represent proliferative zone and thus considered as tumorigenic areas in the liver [31,36]. Formation of such MCF was very much evident in the liver sections at 6th week of AFB1 treatment (Fig.…”

“…Immunohistochemistry for GST-pi, SOD1, and PCNA was performed as described previously [31] with some modifications. Briefly, deparaffinized liver sections were subjected to alcoholic dehydration, inactivation of peroxidases by 3 % H 2 O 2, washing, and finally blocking in 10 % serum solution for 1 h. Sections were then incubated separately with the protein-specific primary antibody (anti-GST-pi, SOD1 and PCNA; 1:100 dilutions) for 2 h in a humidified chamber at room temperature.…”