The effect of androgen deprivation and radiation therapy on an androgen-sensitive murine tumor: an in vitro and in vivo study.

Purpose: 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.

Materials And 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.

Discussion: 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.