Mammary Tumorigenesis in Chemical Carcinogen-treated Mice. VI. Tumor-producing Capabilities of Mammary Dysplasias in BALB/cCrgl Mice

Two types of mammary dysplasias occurring in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/cCrgl mice were transplanted into the cleared mammary fat pads of syngeneic mice for an assessment of their growth behavior and tumor potentials. Keratinized nodules, numerous in DMBA-treated, pituitary isograft-bearing BALB/cCrgl mice, produced primarily ductal outgrowth in control mice and very few tumors (7%) 56 weeks after transplantation. Such dysplasias transplanted into mice bearing pituitary isografts exhibited lobuloalveolar development and produced a higher incidence of tumors (32%). Hyperplastic alveolar nodules (HAN), though relatively rare in DMBA-treated BALB/cCrgl mice, produced lobuloalveolar outgrowth in control mice and had a 100% tumor incidence. Four HAN outgrowth lines were developed by serial transplantation of samples of the nodule outgrowths. The tumor potentials of these nodule lines in intact controls and ovariectomized mice was determined over several transplant generations. The tumor potentials of two of the three nodule lines were decreased in the absence of ovarian hormones. However, the growth of 23 mammary tumors derived from these nodule lines and of nine derived from in situ primary tumors was unaffected by the absence of the ovary. These results, along with those published previously, suggest that mammary tumors in chemical carcinogen-treated mice arise from several precursor populations. These preneoplastic populations comprise both alveolar and ductal hyperplasias.