Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. IV. Induction of Mammary Ductal Hyperplasias2

Abstract

BALB/cCrgl, C57BL/KI, and (C57BL/Ki × DBAf)F₁ mice were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or urethan to determine conditions that would induce a high frequency of ductal hyperplaslas in the mammary gland. Among virgin BALB/c mice treated with either 3.0 or 4.0 mg DMBA, ductal hyperplasias and mammary tumors were present in 50% and 31% of the mice, respectively. These ductal hyperplasias were characterized by intraluminal epithelial hyperplasia and capped by endbud-like structures that appeared abnormal. Hyperplastic alveolar nodules were not seen. Most mammary tumors were adenocarcinomas rather than the adenoacanthomas observed in DMBA-treated, pituitary isograft-bearing BALB/c mice. The predominant mammary lesions in urethan-treated, pituitary isograftbearing C57BL and (C57BL × DBAf)F₁ mice were terminal duct (lobular) hyperplaslas characterized by intraluminal epithelial hyperplasia; the urethan-induced mammary tumors were a mixture of adenocarcinomas (36%), adenoacanthomas (5%), and fibroadenomas (59%). The induction by chemical carcinogens of intraductal hyperplaslas in a relatively high incidence, with associated mammary neoplasms, provides a system for study of the process of tumor progression in lesions similar to suspected high-risk lesions occurring in human breast cancer.