4.0 Article

The MNU Plus Testosterone Rat Model of Prostate Carcinogenesis

Journal

TOXICOLOGIC PATHOLOGY
Volume 50, Issue 4, Pages 478-496

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/01926233221096345

Keywords

prostate cancer; animal model; rat; testosterone; MNU

Funding

  1. NIH/NCI (Texas Tech University) [R01CA43151, R01CA16087, R01 CA76426, R01CA104334, R01 CA172169, P30CA16087]
  2. NCI Division Cancer Prevention [N01-CN-15110, N01-CN-25017, N01-CN-35566, N01-CN-43303, N01-CN-65120, N01-CN-85097, N01-CN-85177, N01-CN-95113, HHSN2612015000421, HHSN2612012000161, 75N91019D00012]

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Animal models of prostate cancer are crucial for identifying chemopreventive treatments. This article introduces a reliable rat model that recapitulates human prostate cancer and has predictive value for human clinical trials. The article describes the induction protocol, diagnostic criteria, and current tumor induction protocol of the model.
Animal models of prostate cancer are essential to identify chemopreventive treatments against this major male malignancy. The N-methyl-N-nitrosourea (MNU) plus testosterone rat model of prostate carcinogenesis is a reliable animal model that recapitulates human prostate cancer in many respects and has been used extensively in chemoprevention studies with good predictive value for the results of human clinical trials. The objective of this article is to describe the induction protocol of this model, demonstrate its robustness and reproducibility over time and across rat strains, provide diagnostic criteria for the identification of prostate lesions, and present the current tumor induction protocol so that others can use this model in a reliable manner. The majority of accessory sex gland tumors in this model are adenocarcinomas originating in the anterior and dorsolateral prostate that metastasize to lungs and abdominal structures. The rat strain used is of critical importance, with the commercially available Wistar WU and Fischer F344 strains yielding the highest tumor incidences. Low dose, long-term testosterone treatment is essential for a high tumor incidence, but in advanced stage, large adenocarcinomas do not appear to be androgen dependent. This rat model is a robust and reproducible prostate cancer animal model of human prostate cancer.

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