Premium
Susceptibility of Lobund–Wistar × Copenhagen hybrid rats to autochthonous prostate carcinogenesis
Author(s) -
Suckow Mark A.,
Wolter William,
Pollard Morris
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20237
Subject(s) - testosterone propionate , prostate cancer , prostate , endocrinology , testosterone (patch) , medicine , seminal vesicle , cancer , andrology , androgen , hormone
BACKGROUND Transplantation of the Dunning R‐3327 prostate tumor cell line is a common model of prostate cancer, though the rat strain (Copenhagen) from which the cell line was derived is resistant to spontaneous and chemically induced prostate cancer. METHODS To determine if susceptibility to chemically induced prostate carcinogenesis can be transferred from the susceptible Lobund–Wistar (LW) rat strain to the resistant Copenhagen (COP) strain, male COP rats and LW × COP hybrids were administered an intravenous dose (30 mg/kg) of methylnitrosourea (MNU) and implanted three times with silastic capsules containing testosterone propionate (25 mg each) at a 2‐month interval. Serum was sampled at 3, 6, 9, and 12 months of age and assayed for testosterone. RESULTS Serum testosterone was significantly but transiently elevated following implantation of capsules with testosterone propionate, but then decreased by 12 months of age to a level which was significantly less ( P ≤ 0.001) than in LW rats but not significantly different from COP rats. Prostate cancer did not develop in COP rats, but 36% of LW × COP hybrids developed prostate–seminal vesicle tumors which expanded into the dorsolateral lobes within 10 months of MNU administration; this compares to 90% of LW rats which develop such tumors following this same induction protocol. CONCLUSIONS COP rats lack inherent susceptibility to development of prostate cancer; susceptibility may be transferred from LW rats, or resistance from COP rats, to LW × COP hybrids and is present in the haploid state, consistent with the two‐mutation event hypothesis of Knudson which holds that two mutations are required at a genetic locus for development of some cancers. © 2005 Wiley‐Liss, Inc.