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Inflammation and Atrophy Precede Prostatic Neoplasia in a PhIP-Induced Rat Model
- Source :
- Neoplasia: An International Journal for Oncology Research, Vol 8, Iss 9, Pp 708-715 (2006)
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclicamine in the human diet and is carcinogenic in the rat prostate. To validate PhIP-induced rat prostatic neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow progressive changes over time. We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at the ages of 25, 45, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P = .002, > .001, and .016 for 25, 45, and 65 weeks, respectively) and atrophy (P = .003, > .001, and .006 for 25, 45, and 65 weeks, respectively) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP-treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase π immunostaining preceding the development of PIN.None of the animals in this study developed invasive carcinomas, differing from those in previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP-treated rat prostate proceeds from inflammation to postinflammatory proliferative atrophy to PIN.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Brief Article
Inflammation
Biology
lcsh:RC254-282
Pathogenesis
Prostate cancer
Atrophy
Prostate
Internal medicine
medicine
Animals
Cell Proliferation
Glutathione Transferase
Prostatic Intraepithelial Neoplasia
Intraepithelial neoplasia
rat model
Imidazoles
Prostatic Neoplasms
Cancer
PhIP carcinogen
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Rats, Inbred F344
Rats
Disease Models, Animal
medicine.anatomical_structure
Endocrinology
prostate inflammation
Carcinogens
medicine.symptom
Immunostaining
Subjects
Details
- ISSN :
- 14765586
- Volume :
- 8
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Neoplasia
- Accession number :
- edsair.doi.dedup.....9568e772d19d93e802c8755a1c4bc421
- Full Text :
- https://doi.org/10.1593/neo.06373