A new approach to mammary tumorigenesis in rodents

Abstract

Most of the mammary tumors in mice and rats arise from recognizable lesions of the mammary gland. The nodule cells are subpopulations of mammary cells which resemble the normal lobules of pregnant mice. They are considered preneoplastic lesions. At least 2 sequential transformations in the process of mammary tumorigenesis occur. The 1st is a change from normal to nodule and the 2nd is a change from nodule to tumor. Experimental material consisted of hyperplastic alveolar outgrowth lines which did not carry the mammary tumor virus MTV or its variant NIV and were not induced by chemical carcinogens or by irradiation. The primary nodules from which the outgrowth lines were developed occurred in BALB/cCrgl and BALB/cAnDe female mice. The BALB/cCrgl donors had been subjected to prolonged hormonal stimulation from pituitary isografts. The others were retired breeders. The tumor incidence of untreated nodule outgrowths maintained in intact BALB/c virgin females varied from 4% to 61%. Ages of onset varied from 8 to 13 months. Oncogenic agents studied with BALB/cCrgl mice were MTV NIV 3-methylcholanthrene (MC) 9 10-dimethyl-1 2-benzanthracene (DMBA) urethan gamma radiation and prolonged hormonal stimulation. These agents induced nodule transformation when applied to the hormonally stimulated female BALB/c mice. Results showed that MTV and NIV were effective agents in neoplastic transformation. MTV was more effective. MC and DMBA and urethan were also effective agents. Gamma radiation produced a small but significant increase in the incidence of tumors and the latent period was reduced. It was thought that attention should be focused on conditions leading to the nodule transformation as well as to the neoplastic transformation. Ability to manipulate the hosts immunologic defense mechanisms should be directed toward the nodule cell population rather than to the already established neoplastic cell population.