DNA synthesis of benign human breast tumors in the untreated athymic "nude" mouse. An in vivo model to study hormonal influences on growth of human breast tissues.

DNA synthesis in 33 human benign breast tissue biopsy specimens (HBT) was determined by 3H-thymidine radioautography 0, 15, 30, and 60 days after s.c. transplantation to female nude mice. A third of the grafts was removed from each mouse at each time period. Grafts and 0-day slices were exposed to 3H-thymidine in vitro. Labeling indices (LI) [number of radiolabeled epithelial cells per unit area epithelium (0.1 mm2)] were calculated for 0-day slices and grafts from each mouse at each time period. The LI of high 0-day HBT grafts (LI greater than 15) decreased significantly between 0 and 15 and 0 and 30 days. The LI of low 0-day HBT grafts (LI less than 15) increased significantly at 15 days then decreased to 0-day levels at 30 days. No significant differences in LI of HBT grafts were observed between 30 and 60 days. Thus, a model has been proposed for studies of factors effecting the growth of human breast tissues transplanted to nude mice in which (1) each mouse is used as its own control by measuring DNA synthesis of grafts before and after treatment, and (2) the treatment is initiated 30 days or more after transplantation of breast tissues when graft DNA synthesis is stabilized. Using this model, we have observed marked increases in HBT graft DNA snythesis induced by human placental lactogen treatment of host nude mice from day 42 to day 60 after HBT transplantation.