Early increases in ribonucleic acid polymerase activities of dimethylbenzanthracene-induced mammary tumour nuclei in response to oestradiol-17beta and tamoxifen.

Studies on the mode of action of tamoxifen have shown that this compound ultimately causes regression of mammary tumours induced in female rats by 7,12-dimethylbenz(a)-anthracene, but induces preliminary effects similar to those produced by oestradiol-17beta. Following a single intravenous injection of either substance, a sequence of events was observed which included depletion of cytoplasmic receptor, a concomitant increase in nuclear receptor and a subsequent replenishment of cytoplasmic receptor. Tamoxifen and oestradiol-17beta induced a transient increase in RNA polymerase B activity, followed by increases in RNA polymerase A and, again, RNA polymerase B activity. Tamoxifen, unlike oestradiol-17beta, could not maintain replenishment of cytoplasmic receptor, the increase in RNA polymerase A activity or the secondary rise in RNA polymerase B activity. The basic anti-oestrogenic properties of tamoxifen may be implicit in its inability to maintain oestrogen stimulation, and may be linked to its retention time within the nuclei.