Journal article
Comparison of different initiation protocols in the resistant hepatocyte model
Toxicology (Amsterdam), Vol.206(3), pp.373-381
2005
DOI: 10.1016/j.tox.2004.07.014
PMID: 15588927
Abstract
Several models in rat liver have been developed to study multistage carcinogenesis, including the Solt–Farber resistant hepatocyte model. In this model, initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). As an alternative to PH, we investigated two different procedures: fasting for 96
h followed by refeeding, or the use of one-day-old neonates. Male Fisher 344 rats were injected p.o. with diethylnitrosamine (DEN) (0, 20, or 100
mg/kg) 24
h after refeeding or PH (controls received DEN alone with no proliferative stimulus). For the neonatal group, male and female Fisher 344 rats were treated with DEN (0 or 20
mg/kg, i.p.) at one day of age. All initiated animals were treated at the same age (11 weeks) with the following selection agents: three daily doses of 2-acetylaminofluorene (AAF) (30
mg/kg), followed by a single dose of carbon tetrachloride (2
ml/kg), followed by three additional daily treatments of AAF (30
mg/kg). Rats were euthanized 2 weeks after the last AAF injection. The PH, neonatal male, and neonatal female groups receiving DEN developed more γ-glutamyl transpeptidase (GGT)-positive foci per cubic centimeter and foci per liver as compared to untreated rats receiving the same proliferative stimulus, whereas the fasting/refeeding group and the group receiving no proliferative stimulus did not. All DEN-treated groups receiving one of the proliferative stimuli had more foci per cubic centimeter than the DEN-treated group receiving no proliferative stimulus. The volume fractions of GGT-positive foci in the PH/DEN and neonatal male/DEN groups were higher than those of both the DEN-treated group receiving no proliferative stimulus and the groups receiving the same proliferative stimulus without DEN. In neonatal females-receiving DEN, the volume fraction was not different from either neonatal females not receiving DEN or DEN-treated rats receiving no proliferative stimulus. The volume fraction in the fasting/refeeding group was increased when DEN was administered at 100
mg/kg but not at 20
mg/kg. We conclude that the use of male neonatal rats can replace the PH in the Solt–Farber protocol. Fasting/refeeding was also effective at increasing the volume fraction of GGT-positive foci, but only at the higher dose of DEN.
Details
- Title: Subtitle
- Comparison of different initiation protocols in the resistant hepatocyte model
- Creators
- Parvaneh Espandiari - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, USALarry W Robertson - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, USACidambi Srinivasan - Department of Statistics, University of Kentucky, Lexington, KY 40506, USAHoward P Glauert - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, USA
- Resource Type
- Journal article
- Publication Details
- Toxicology (Amsterdam), Vol.206(3), pp.373-381
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.tox.2004.07.014
- PMID
- 15588927
- ISSN
- 0300-483X
- eISSN
- 1879-3185
- Language
- English
- Date published
- 2005
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002458202771
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