Susceptibility of the mammary gland to carcinogenesis. III. The cell of origin of rat mammary carcinoma.
The rat mammary gland epithelium is composed of three cell types: dark cells (DCs), intermediate cells (ICs), and a layer of myoepithelial cells (MCs), which are evenly distributed along the mammary gland tree in rather constant proportions. The present study was carried out for a determination of the effect of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) on the distribution and proliferative activity of these cell populations. The proportion and the DNA labeling index (DNA-LI) of each cell type were determined in terminal end buds (TEBs), terminal ducts (TDs), alveolar buds (ABs), and alveoli of the normal Sprague-Dawley rat mammary gland and in intraductal proliferations (IDPs) and carcinomas removed at selected intervals after DMBA administration. DMBA-induced changes in cell distribution were limited to TEBs and TDs, whereas ABs and alveoli were unaffected. The alterations consisted in an increment in ICs from 11% in TEBs and TDs to 90% in tumors and a decrease in DCs from 77% in TEBs and TDs to 7% in tumors. MCs were relatively unaffected. The DNA-LI of DCs, which in the normal gland TEB was 14%, was depressed by DMBA to 6%, whereas the DNA-LI of ICs remained unchanged from the basal level of 40% during the process of carcinogenesis. The progressive increment in number of ICs with a steady DNA-LI suggested that the IC is the target cell of the carcinogen and the cell of origin of mammary carcinomas.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage; D000230:Adenocarcinoma / Q000139:chemically induced / Q000648:ultrastructure*; D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000139:chemically induced / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000378:metabolism; D004198:Disease Susceptibility; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D008321:Mammary Glands, Animal / Q000648:ultrastructure; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains
D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA