Subcutaneous implant assays

Fifteen ewes were subcutaneously implanted with 0 to 10 cm of silicone implants containing testosterone propionate. The implants were made as described in Experiment 1. Implants were subcutaneously implanted in the axilla. Blood plasma was collected before and 13 days after implantation and assayed for plasma testosterone concentrations by a validated testosterone enzyme immunoassay (described later). 

Five beef females were implanted with silicone implants containing testosterone propionate. Implants were made from silicone tubing (9.5 mm i.d., 12.7 mm o.d.). A polystyrene rod (4.8 mm in diameter) was fixed in the center of the implant in order to reduce the amount of testosterone propionate required to fill the implants. Two heifers were subcutaneously implanted with 22.5 cm of implants and three heifers were implanted with 45.0 cm of implants. Two blood samples were subsequently collected from each heifer and assayed for plasma testosterone concentrations via a validated enzyme immunoassay (described later). Implants were numbered and weighed both before implantation and after implant removal and secretion rate of testosterone propionate from the implants determined. 

At the in vivo assay level, the classic ip-ip (iateraperitoneal) in vivo model has been replaced as a selection criteria for advancement of new dmg candidates to clinical trial. More stringent alternative models iaclude subcutaneous or subrenal capsule implantation of tumor followed by iatravenous dmg dosiag (7) and the human tumor xenograft models ia aude mice (8). 

Fig. 2. Matrigel plug assay results. Matrigel was implanted subcutaneously into athymic mice on d 0 (8-10 mice per group). Daily BMS-275291 oral treatments began on d 0 and continued to d 6. Matrigel plugs were harvested on d 7 and processed for histochemical analyses. Results are expressed as % Inhibition SE (% Relative to Untreated Control).

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