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 tumo r eradication by irradiation can be enhanced by prior androgen depriva tion in an androgen-dependent rodent tumor model. MATERIALS AND METHOD S The androgen-sensitive Shionogi SC-115 mouse mammary carcinoma was g rown in athymic male NCr/Sed (nu/nu) mice and in culture. An androgen- deprived environment was created in vivo by surgical orchiectomy and i n vitro through the use of charcoal-stripped androgen-free medium. The dose of radiation required to control 50% of tumors (tumor control do se [TCD50] assay) was used to assess the radiation response of tumors grown in vivo. Colony-formation assays were used for in vitro assessme nt. RESULTS After orchiectomy, Shionogi tumors regress in volume quick ly but inevitably regrow as androgen-insensitive clones. The TCD50 for G-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 4 8 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 ra diation sensitivity induced by prior androgen deprivation, although th ere was a trend toward lower D-0 values with increasing duration of de privation. 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 nutr itional status of a smaller tumor, but changes in intrinsic radiation sensitivity cannot be excluded.