An Autoradiographic Study of the Early Effects of 7,12-Dimethylbenz(a)anthracene and Progesterone on DNA Synthesis in Rat Mammary Epithelial Cells and Subsequent Tumour Development

Abstract

Experiments were undertaken to investigate the early effects of DMBA or progesterone, or the two in combination, on DNA synthesis in rat mammary epithelial cells, and also to determine whether there was any correlation between the level of DNA synthesis observed in the first 96 hours after administration of DMBA, either alone or combined with progesterone, and subsequent tumour development. It was found that DMBA alone caused an insignificant reduction in DNA synthesis in the first 96 hours, whereas progesterone significantly enhanced DNA synthesis. When the carcinogen and hormone were administered together, a greater rise was seen in the level of DNA synthesis than that occurring in rats treated only with DMBA, but the increase was not significantly greater than that in untreated animals. A two-way analysis of variance revealed no interaction between DMBA and progesterone in relation to mammary epithelial cell DNA synthesis. Mammary neoplasms occurred only in the groups of rats which had received DMBA, either alone or in combination with progesterone. No correlation could be demonstrated between the extent of DNA synthesis observed in mammary glands biopsied between 6 and 96 hours after carcinogen administration and the occurrence of tumours in the host rats 135 days later.