EFFECT OF HORMONE DEPLETION ON CELL-SURVIVAL IN THE EMR-86 RAT MAMMARY-CARCINOMA

Growth of the transplantable EMR-XS rat mammary carcinoma depends on e levated prolactin levels which are induced by oestrogenic stimulation of the pituitary. We investigated histological and cell kinetic change s during tumour regression after removal of implanted oestrogen pellet s (EP), and we especially focused on the role of apoptosis. After EP r emoval, serum prolactin decreased to basal levels in 5 days, reaching its largest depletion during the first day. Similarly, S-phase cell fr actions, assessed by bromodeoxyuridine (BrdUrd) incorporation, decreas ed to half the initial value during the first day and developed into a gradual decrease to basal levels thereafter. Within 10 days, tumour v olumes were reduced to 20% without striking changes in tissue architec ture. To quantify apoptosis, we applied a method that stains DNA break s in tissue sections and subsequently measured the stained area by aut omated image cytometry. This procedure was necessary, as the subtle ch anges could not be detected by histological examination alone, One day after the rapid decline of the S-phase Fraction. a 3-fold increase in apoptotic area was observed that remained for about 3 days and then g radually decreased. This correlated with the histologically observed r eduction of tumour cells. In spite of the major cell loss, regression came to a halt after about 10 days. The surviving cell fraction is dis cussed within the contest of a stem cell hypothesis, in which tumour c ells with stem cell characteristics are Less susceptible to hormone-in duced apoptosis than their (non-stem) daughter cells. This notion has implications for the eradication of residual tumour cells. because a d iminished susceptibility might also apply to apoptosis induced by radi o- or chemotherapy.