Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment

Background: Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the appearance of altered hepatocyte foci (FAH). Aims: We compare two initiation-promotion models to evaluate the presence of FAH or additional hepatic pathologies in which other organs were affected up to five month post treatment. Material and methods: FAH were induced in male adult Wistar rats with two doses of dietylnitrosamine (DEN, 150 mg/kg bw) followed by 4 doses per week (3 weeks) of 2-acetylaminofluorene (2-AAF, 20 mg/kg bw) or with one dose of DEN (200 mg/kg bw) followed by 2 doses per week (3 weeks) of 2-AAF. DEN 150, DEN 200 and control rats (received the vehicle of the drugs) groups were compared. Rats were euthanized immediately after the last dose of 2-AAF, at 3, 4 and 5 months (n = 3 for euthanasia times per group). Samples of livers, lungs, kidneys, pancreatic tissue and small bowel were processed for histological and immunohistochemical analysis. Results: FAH persisted for 5 months in all livers of the DEN groups. Three months after withdrawal of 2-AAF, one rat from DEN 150 group developed fibrosis and 5 months after 2-AAF removal another rat from the same group presented a microscopic hyperplastic nodule. Only the lungs had damages compatible with lesions induced by gavage-related reflux in DEN groups. Conclusion: We concluded that up to five month post treatments, FAH persisted in all the livers from DEN groups; livers from DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups