Chemical Carcinogenesis in C3H/StWi Mice, A Worthwhile Experimental Model for Breast Cancer¹ Free

The C3H/StWi mouse subline spontaneously lost the mouse mammary tumor virus in 1958 and became a low mammary cancer strain. Previous studies have shown that StWi mice are highly susceptible to mouse mammary tumor virus (MMTV)(standard) but less so to infection with MMTV(low oncogenic). Unlike C3Hf mice, StWi virgin females and their F₁ hybrids with BALB/c/He mice do not develop mammary cancer when exposed to increased estrogenic stimulation (20% diethylstilbestrol pellets). In contrast, after treatment with 7,12-dimethylbenz(α)-anthracene, (DMBA), 46% (17 of 37) developed mammary cancer at an average age of 7.8 months (range, 4.5 to 10 months). The tumors were mainly papillary adenocarcinomas. Mammary dysplasias were found in 73% of the whole-gland mounts examined at 10 months (3.6/mouse). All but three dysplasias were ductal in origin. No hyperplastic alveolar nodules were found. Electron microscopic examination of 14 DMBA-induced tumors failed to reveal the presence of type A or B particles; however, 11 of 14 tumors contained budding and extracellular type C virions. Evaluation of five DMBA-induced mammary tumors for MMTV-specific RNA sequences indicated levels as low or lower than found in the mammary glands of old retired multiparous C3H/StWi females (0.0035%). Much higher levels (0.2 to 0.4%) of MMTV-specific RNA to total RNA occurred in MMTV-induced C3H/StWi mammary tumors. These results and others suggest that the StWi subline may represent a unique model for the study of viral, chemical, and viral-chemical interactions in the malignant transformation of mammary epithelial cells. Studies are currently in progress to evaluate the effect of the presence of MMTV on the response of C3H/StWi mammary glands to DMBA and to screen the DMBA-induced tumors by immunoperoxidase for the expression of MMTV-specific antigenic determinants.