Mammary tumors in inbred Fischer 344 female rats were induced by 7, 12-dimethylbenz[α]anthracene (DMBA). Primary tumors were excised and transplanted subcutaneously to syngeneic recipients. The transplanted tumors, thus developed, were used for further serial transplantation of up to five passages. Tumors serially transplanted into intact recipients were able to grow to 1.5-2 cm in diameter within 1-2 months. Histologically, tumor tissues of early passages were characterized by mixed populations of epithelial and spindle cells while tumors of late passages contained only the spindle cells. Tumors grafted into ovariectomized hosts were not able to grow in the first and second passages, although they remained viable, since estrogen therapy was able to activate their growth. By the third passage, tumors were able to grow when transplanted into ovariectomized recipients but the growth rate was considerably slower than that in the intact hosts. In the fourth and fifth passages, tumors transplanted in ovariectomized recipients grew as well as those in intact hosts. Tumors grown under these hormone deficient conditions consisted mainly of spindle cells. Following the establishment of the transplanted tumors, ovariectomy in the hosts resulted in an initial regression and subsequent regrowth of tumors of early passages and had no effect on those of late passages. Again, the long-term growth of transplanted tumors in ovariectomized hosts was associated with an increase in the spindle cell population which gradually replaced the regressed epithelial cells. Contents of estrogen receptors were high in the primary tumors, averaging 45 ± 9 fmol/mg protein (mean ± S.E.M.) and were low in the late passages, being 5.2 ± 0.7 fmol/mg. Activities of acid ribonuclease were high in primary tumors (1132 ± 163 units/mg protein), decreased in tumors of the fifth passage (387 ± 51 units/mg protein) and reached the lowest value in tumors of the first passage following regrowth in ovariectomized hosts (301 ± 50) units/mg protein). Results suggest that the so-called 'hormone-dependent' DMBA-induced mammary tumors consist of at least two histologically and biochemically distinct cell types, hormone-dependent epithelial and hormone-independent spindle-shaped cells, and that the latter are selected over the epithelial component during serial transplantations or under unfavourable hormonal conditions due to ovariectomy in the hosts.
ASJC Scopus subject areas