DNA Labeling Index and Structure of the Rat Mammary Gland as Determinants of Its Susceptibility to Carcinogenesis2

Abstract

In a study of 7,12-dimethylbenz[a]anthracene (OMBA)-induced rat mammary carcinomas, which arise from the terminal end-buds (TEB) and terminal ducts (TD) of the mammary gland, and benign lesions such as hyperplastic alveolar nodules and adenomas, which arise from the alveolar buds (AB) of the gland, we correlated the number of TEB, TD, and AB and their DNA labeling indexes at the time of DMBA administration with the number and type of mammary gland tumors induced by the carcinogen. Young virgin (55-day-old), old virgin (180-day-old), and multiparous (180-day-old) noninbred Sprague-Dawley rats were inoculated iv with [³H]thymidine. Simultaneously, a similar group received one intragastric dose of DMBA. The group given [³H]thymidine was killed 1 hour after injection. All mammary glands were processed for either wholemount or autoradiography. The number of TEB, TD, AB, and lobules per square millimeter were counted in wholemount preparations, and the DNA labeling index in the epithelial cells of these structures was determined. These results were compared with the number and type of tumors developed by the animals of the second group. The mammary glands of young virgin rats that contained the highest number of TEB, TD, and labeled cells had 100% incidence of carcinomas. The glands of old virgin rats had fewer TEB and TD and fewer labeled cells, and these rats developed fewer carcinomas (63%). Glands of multiparous rats contained no TEB, a small number of TD, and few labeled cells; these rats had the lowest Incidence of carcinomas (21%). The results demonstrated that the susceptibility to carcinogens is correlated to the density of TEB and TD and their DNA labeling indexes.