M Pollard1. 1. Lobund Laboratory, University of Notre Dame, Indiana 46556, USA.
Abstract
BACKGROUND: Gene-regulated mechanisms govern tumor development, but the actual development of tumors can be suppressed or promoted by epigenetic factors. Lobund-Wistar (L-W) rats are genetically predisposed to development of spontaneous and induced metastasizing moderately differentiated adenocarcinomas in the prostate-seminal vesicle (P-SV) complex. In L-W rats with one slow-release subcutaneous implant of dihydrotestosterone (DHT) (5alpha-Androstan-17beta-ol-3-one), the development of induced P-SV tumors 14 months later was significantly suppressed, with involution of testes, aspermia, and absence of detectable serum testosterone. The tumor-suppressive effect of DHT was confirmed. Spontaneous P-SV tumors developed in 57 of 220 control L-W rats (26%) at an average age 20 months. METHODS: At age 12 months, 70 L-W rats were administered an implant of 40 mg of DHT, and 75 untreated rats served as controls. All rats that developed palpable P-SV tumors were autopsied, and surviving rats were autopsied at age 24 months. RESULTS: At age 24 months, 9 of 70 DHT-treated rats (12.8%) and 20 of 75 DHT-free control rats (26.6%) had developed P-SV tumors spontaneously at average age 20.5 and 20 months, respectively. CONCLUSIONS: Slow-release implants of DHT administered to L-W rats at age 12 months reduced by 50% the development of spontaneous P-SV tumors by age 24 months.
BACKGROUND: Gene-regulated mechanisms govern tumor development, but the actual development of tumors can be suppressed or promoted by epigenetic factors. Lobund-Wistar (L-W) rats are genetically predisposed to development of spontaneous and induced metastasizing moderately differentiated adenocarcinomas in the prostate-seminal vesicle (P-SV) complex. In L-W rats with one slow-release subcutaneous implant of dihydrotestosterone (DHT) (5alpha-Androstan-17beta-ol-3-one), the development of induced P-SV tumors 14 months later was significantly suppressed, with involution of testes, aspermia, and absence of detectable serum testosterone. The tumor-suppressive effect of DHT was confirmed. Spontaneous P-SV tumors developed in 57 of 220 control L-W rats (26%) at an average age 20 months. METHODS: At age 12 months, 70 L-W rats were administered an implant of 40 mg of DHT, and 75 untreated rats served as controls. All rats that developed palpable P-SV tumors were autopsied, and surviving rats were autopsied at age 24 months. RESULTS: At age 24 months, 9 of 70 DHT-treated rats (12.8%) and 20 of 75 DHT-free control rats (26.6%) had developed P-SV tumors spontaneously at average age 20.5 and 20 months, respectively. CONCLUSIONS: Slow-release implants of DHT administered to L-W rats at age 12 months reduced by 50% the development of spontaneous P-SV tumors by age 24 months.