The effect of androgen deprivation and radiation therapy on an androgen-sensitive murine tumor: an in vitro and in vivo study.
OBJECTIVE
The purpose of this research was to assess whether or not tumor eradication by irradiation can be enhanced by prior androgen deprivation in an androgen-dependent rodent tumor model.


METHODS
The androgen-sensitive Shionogi SC-115 mouse mammary carcinoma was grown in athymic male NCr/Sed (nu/nu) mice and in culture. An androgen-deprived environment was created in vivo by surgical orchiectomy and in vitro through the use of charcoal-stripped androgen-free medium. The dose of radiation required to control 50% of tumors (tumor control dose [TCD50] assay) was used to assess the radiation response of tumors grown in vivo. Colony-formation assays were used for in vitro assessment.


RESULTS
After orchiectomy, Shionogi tumors regress in volume quickly but inevitably regrow as androgen-insensitive clones. The TCD50 for 6-mm Shionogi tumors grown in intact mice was 89.0 Gy (95% confidence intervals [CI]: 83.4 to 94.9). When orchiectomy was performed 24 to 48 hours prior to irradiation, the TCD50 fell to 60.3 Gy (95% CI: 54.8 to 66.3). When irradiation was withheld until maximum tumor regression following orchiectomy, it was lower still-42.1 Gy (95% CI: 37.4 to 47.4). In vitro studies demonstrated no profound changes in intrinsic radiation sensitivity induced by prior androgen deprivation, although there was a trend toward lower Dzero values with increasing duration of deprivation.


CONCLUSIONS
Prior androgen deprivation enhances the ability of irradiation to eradicate Shionogi tumors in vivo. It is likely that this effect results from cytoreduction and/or improvement in the nutritional status of a smaller tumor, but changes in intrinsic radiation sensitivity cannot be excluded.
Zietman
A L
AL
Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Nakfoor
B M
BM
Prince
E A
EA
Gerweck
L E
LE
D000728:Androgens; D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D009919:Orchiectomy; D013739:Testosterone / Q000097:blood; D014407:Tumor Cells, Cultured
D000728:Androgens; D013739:Testosterone