T. Granfors et al., After radiotherapy testosterone stimulation is unable to increase growth in the Dunning R3327-PAP prostate tumour, UROL RES, 27(5), 1999, pp. 357-361
A study was carried out to investigate whether testosterone treatment is ab
le to influence tumour growth in a rat prostatic adenocarcinoma previously
treated with castration and high-dose fractionated irradiation. Copenhagen
x Fisher rats bearing the androgen-sensitive, well-differentiated Dunning R
3327-PAP tumour were castrated and thereafter treated with external beam ra
diation with photons from a 4-MV linear accelerator. One month after irradi
ation, substitution with subcutaneous testosterone was started. Tumour volu
mes and rat weights were monitored up to 256 days after castration, and at
the end of the study a microscopic analysis of the tumours was performed. I
rradiation delayed tumour growth as compared with untreated tumours. Castra
tion delayed tumour growth, but a hormone-refractory relapse to doubled tum
our volume was seen within 45 days. If testosterone was added after castrat
ion, the tumours grew rapidly. However, testosterone failed to increase tum
our growth when given to rats treated with orchiectomy and irradiation. His
tological examination showed that the irradiated tumours still contained tu
mour epithelial cells, but these cells apparently do not respond to testost
erone stimulation. The well-differentiated and androgen-sensitive rat prost
atic adenocarcinoma did not grow after irradiation despite stimulation with
testosterone. This indicates that the malignant cells lose their androgen
sensitivity after high-dose irradiation.