title: Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment.
abstract: BACKGROUND
  Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the appearance of altered hepatocyte foc (FAH).
  
  
  OBJECTIVE
  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.
  
  
  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 mice (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 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 the 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 damage compatible with lesions induced by gavage-related reflux in DEN groups.
  
  
  CONCLUSIONS
  We concluded that up to five month post treatments, FAH persisted in all the livers from the DEN groups; livers from the DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups.
authors.affiliation: Area Morfología, Dto de Ciencias Fisiológicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
authors.forename: Gerardo Bruno
authors.initials: GB
authors.lastname: Pisani
authors.affiliation: Escuela de Medicina, Area Patología, Universidad Abierta Interamericana, Argentina.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Valenti
authors.affiliation: AREA MORFOLOGIA, DTO CIENCIAS FISIOLÓGICAS, Facultad de Ciencias Bioquímicas y Farmacéuticas, ARGENTINA.
authors.forename: Alejandra Beatriz
authors.initials: AB
authors.lastname: Quintana
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D002273:Carcinogens; D004052:Diethylnitrosamine; D022781:Hepatocytes / Q000473:pathology; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D008168:Lung / Q000473:pathology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene