Organ culture passage enhances the oncogenicity of carcinogen-induced hyperplastic mammary nodules

Summary The purpose of this study was to determine whether culturing hyperplastic mammary nodules in hormone-free medium would enhance their oncogenicity following subsequent transplantation into mammary fat pads. The underlying hypothesis is that the proliferation of transformed cells within the nodules is inhibited by hormone-dependent normal cells also present in the nodules. Accordingly, both primary hyperplastic nodules and tissues from a hyperplastic outgrowth of a primary nodule were maintained as organ cultures for varying periods in hormone-free Medium 199. The results show that whereas noncultured nodules developed mammary tumors at an incidence of only 15%, those passaged in organ culture gave rise to mammary tumors at an incidence of 40 to 43%. This threefold enhancement in the oncogenicity of mammary nodules is interpreted to be due, at least in part, to a reduction in the normal mammary cell content of nodules. Consistent with this interpretation is the observation that cultured nodules gave rise to mammary outgrowths that were predominantly hyperplastic, whereas noncultured nodules generated outgrowths with varying proportions of hyperplastic and normal ductal mammary tissue. This investigation was supported by National Cancer Institute Grant CA-17862.