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Successful Transplantation of Human Benign Breast Tumors into the Athymic Nude Mouse and Demonstration of Enhanced DNA Synthesis by Human Placental Lactogen¹

Department of Anatomy, Michigan State University, East Lansing, Michigan 48824

Each of 10 biopsy specimens of benign human breast tumors, obtained from 10 patients, was cut into slices (30 slices/specimen) and transplanted s.c. into 3 female athymic nude mice (30 mice, 10 grafts/mouse). Of the 3 mice in each of the 10 triads, 2 mice were intact and 1 mouse was ovariectomized 30 days before transplantation. Ten days after transplantation the following s.c. injections were administered twice dally for 20 days: 0.9% NaCl solution to one intact and one ovariectomized mouse and 0.5 mg of human placental lactogen in 0.9% NaCl solution to one intact mouse of each triad. On the 20th day of injections each mouse received an i.p. injection of [³H]thymidine and was sacrificed 1 hr later. Grafts were removed and processed for histological and autoradiographical analyses. Evaluation of DNA synthesis was obtained by counting the total number of [³H]thymidine-labeled epithelial cells in 6 sections obtained from each graft.

All ten of the biopsy specimens, regardless of host hormonal treatment, were accepted and maintained by these mice. The grafts retained their original morphology. The ductal epithelium of these grafts were shown to synthesize DNA, an activity that was significantly increased by human placental lactogen. Ovariectomy did not significantly influence the mean incorporation of [³H]thymidine into DNA. These results provide evidence that human placental lactogen is a direct stimulant of DNA synthesis of the ductal epithelium found in benign human breast tumors. In addition, the athymic nude mouse appears to be a promising, valuable tool for the in vivo study of factors influencing the development and growth of the human breast.

¹ Supported in part by Research Grant BC-220C from the American Cancer Society.

² To whom requests for reprints should be addressed.

Received 10/11/77. Accepted 4/25/78.